Evaluation of the Therapeutic Effect of Pulmonary Embolism by CT Pulmonary Angiography Combined With Clinical Indexes

Background To evaluate the value of CT pulmonary angiography (CTPA) in evaluating the therapeutic ecacy of pulmonary embolism (PE) through the study of CT pulmonary artery obstruction index (PAOI), right ventricular function parameters and some clinical indexes related to coagulation function and cardiac function injury. Select 30 patients with pulmonary embolism who underwent CTPA examination before and after treatment in our hospital, sort out their CTPA images before and after treatment, and obtain PAOI and right heart function parameters, including ascending aorta diameter (AAd), main pulmonary artery diameter (MPAd), ratio of main pulmonary artery diameter to ascending aorta diameter (MPAd/AAd), right pulmonary artery trunk diameter (RPAd), left pulmonary artery trunk diameter (LPAd), the ratio of the maximum short axis diameter of the right ventricle to the maximum short axis diameter of the left ventricle (RVd/LVd), and calculate the pulmonary artery obstruction index (PAOI).At the same time obtain the required clinical indicators, including serum D-dimer, N-terminal B-type natriuretic peptide precursor (NT-proBNP), cardiac troponin I (cTnI), myocardial enzyme prole (aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK)). function and therapeutic ecacy.


Introduction
PE is a serious venous thromboembolic disease (VTE), which can cause fatal complications. It is an important cause of death of cardiovascular related diseases. The mortality of PE patients in the rst month is about 10% to 30%. In the past decades, the use of thrombolysis, anticoagulation therapy and surgical intervention has increased, which has led to a signi cant improvement in the prognosis of PE patients [1][2][3]. In recent years, the annual incidence rate of PE and the mortality rate related to PE have increased exponentially with age. Therefore, with the aging of the world population, the burden of PE on the society continues to increase [4]. With the continuous development of imaging technology, CTPA can not only intuitively detect the emboli in the arterial lumen, but also qualitatively and quantitatively diagnose the disease. This study used CTPA to obtain the right ventricular function parameters before and after treatment, and compared them with relevant clinical indicators, aiming to better evaluate the effect of pulmonary embolism treatment in imaging, so as to provide more basis for clinical evaluation and prognosis of pulmonary embolism.

General information
In total we identi ed 30 patients in our hospital who underwent CTPA examination and diagnosed PE in our hospital from January 2015 to December 2020, and received anticoagulant or thrombolytic therapy, and then perform the second CTPA examination 1-3 months after treatment.At the same time collecting some clinical indexes related to coagulation function and cardiac function injury within 24h before and after CTPA examination. Among them, there were 18 males and 12 females, aged 13-83 years old, with an average of (52.67±16.67). There has been no serious heart and pulmonary vascular disease and liver and kidney damage. The study was approved by the Institutional Review Board of the hospital, and informed consent was obtained from each patient. Equipment CTPA examination equipment: Philips brilliance ICT 256 slice spiral CT and EBW workstation Evaluate the patient's physical condition before the examination, perform routine iodine allergy tests, and introduce the purpose, methods and precautions of the CTPA examination to the patient or their family members, and sign an informed consent form. Instruct the patient to carry out breath-holding training.
Each breath-holding time is more than 10s. The patient is placed in a supine position, holding the head with both hands, and the scanning direction is from foot to head.
Scanning range: chest entrance to diaphragm level.
The scanning parameters are as follows: tube voltage 120kv, current 250mAs, 0.5s/turn, pitch 0.625, inject iopromide (Uvixine (350mgI/ml)) through the anterior elbow vein with a double-barreled highpressure syringe, the injection rate is 5ml/s , the total dose is 60-80ml, after the contrast agent is injected, the same ow rate is injected with the same ow rate of 0.9% sodium chloride 30ml. The delay time is based on the arti cial intelligence trigger scan, the position is set in the main lung, and the pulse trigger threshold is set to 100HU. After scanning, the reconstructed image has a layer thickness of 0.625mm and a layer spacing of 0.625mm.The data are transmitted to the post EBW processing workstation for analysis.

Statistics indicators
Using Qanadli embolism index [5], the calculation method is as follows, according to the two lungs are divided into 10 pulmonary segment arteries, a partial pulmonary artery blockage is counted as 1, the complete blockage is counted as 2, and when no emboli is found, it is counted as 0. Embolism in subsegment pulmonary artery is calculated based on partial blockage of corresponding pulmonary artery,The embolism in the artery above the pulmonary artery is equal to the total number of its branch pulmonary artery. For example, partial embolism of upper lobe pulmonary artery was 3 points, complete embolism was 6 points, right middle lobe and left lingual lobe pulmonary artery embolism was 2 or 4 points, bilateral lower lobe pulmonary artery embolism was 5 or 10 points, bilateral main pulmonary artery embolism was 10 or 20 points, main pulmonary artery embolism was 20 points, maximum occlusion score was 40 points. Therefore, Qanadli embolism index = ∑(n×d)/40×100%, where n represents the location of the obstruction with emboli, and d represents the degree of obstruction score.
Measure the maximum distance from the ventricular septum to the inner side of the free wall of the ventricle on the patient's CTPA axial image, that is, the diameter of the largest short axis of the ventricle, and calculate the ratio of the maximum short axis diameter of the right ventricle to the maximum short axis diameter of the left ventricle (RVd/ LVd), simultaneously measure the diameter of the ascending aorta (AAd), the diameter of the main pulmonary artery (MPAd), the diameter of the right pulmonary artery (RPAd), and the diameter of the left pulmonary artery (LPAd), and calculate the diameter of the ascending aorta (AAd) and the diameter of the main pulmonary artery (MPAd) ) Ratio (AAd/MPAd).
Collect the clinical indicators required within 24 hours before and after the CTPA examination of the patient, including serum D-dimer, N-terminal B-type natriuretic peptide precursor (NT-proBNP), cardiac troponin I (cTnI), myocardial enzyme pro le (aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK).
Statistical analysis of data CT PAOI and CTPA right heart function parameters were completed by two senior diagnostic imaging physicians who read the CTPA images of the patient without knowing the clinical data of each patient, independently and blindly. The nal results are subject to the consensus of the two physicians.Statistical analysis uses SPSS23.0 statistical software to analyze the data. The measurement data is expressed as x±s and [M(P25,P75)]. The K-S test is used to determine whether the measurement data conforms to the normal distribution. the two paired sample t test is used for those conforming to the normal distribution, and the nonparametric Wilcoxon signed rank sum test is used for those not conforming to the normal distribution, with P < 0.05 as the difference is statistically signi cant. Spearman rank correlation coe cient was used to evaluate the correlation between CT PAOI and RVd / LVd, AAd, MPAd, D-dimer, cTnI, NT-proBNP, AST, LDH, CK. The number and degree of obstructive pulmonary segments in 30 patients before and after treatment are shown in Table 1, After treatment, CTPA showed that the area of pulmonary embolism was signi cantly reduced, and the total number of obstructive pulmonary segments, including incomplete and complete obstructive pulmonary segments, was decreased compared with that before treatment.  Table 2. After thrombolytic or anticoagulant therapy, most of the patients' condition improved signi cantly the comparison of CTPA before and after treatment is shown in (Fig. 1). Two patients' condition did not improve signi cantly after treatment, and three patients' pulmonary artery did not show obvious abnormality when they were reexamined CTPA after treatment. Compared with before treatment, some right ventricular function parameters and clinical indexes were signi cantly different. MPAd, RPAd, LPAd, RVd / LVd, PAOI, D-dimer, NT-proBNP, cTnI, CK, LDH, AST had signi cant changes after treatment (P < 0.05), while other parameters had no signi cant differences before and after treatment (P > 0.05). The correlation between PAOI and right ventricular function parameters and clinical indexes in PE patients is shown in Table 3. PAOI was positively correlated with RVd/ LVd, MPAd and D-dimer, and the correlation coe cient ranged from 0.281 to 0.423. Among them, PAOI had the closest correlation with Ddimer, and the correlation coe cient was 0.423. The correlation scatter diagram was shown in (Fig. 2);

Results
There was no signi cant correlation with other indexes observed.

Discussion
In recent years, the incidence of pulmonary embolism has been increasing, and the early signs and clinical symptoms are atypical. The clinical manifestations can range from occasional asymptomatic subsegmental pulmonary embolism to massive pulmonary embolism that causes cardiogenic shock and multiple organ failure [6]. The embolus obstruction of the pulmonary artery can cause patients to develop pulmonary hypertension and increase the pressure load of the right ventricle, and eventually lead to right ventricular dysfunction (RVD) in some patients, which becomes the main lethal complication of the disease. About 45% of patients with acute PE will suffer from acute right ventricular failure, and as many as 3.8% of patients will develop chronic thromboembolic pulmonary hypertension (CTEPH), and then develop severe chronic heart failure [7]. CTEPH is a relatively common and serious long-term complication in PE patients diagnosed for the rst time [8,9]. Therefore, early diagnosis, timely thrombolysis, anticoagulation therapy, and evaluation of the recovery of pulmonary vascular patency are the focus of treatment of the disease. CTPA is often used as the gold standard for the diagnosis of pulmonary embolism in clinical practice, which can realize qualitative and quantitative diagnosis while visually discovering emboli.
PAOI has important clinical value in evaluating the severity of PE patients. Qanadli et al. proposed that on the basis of CTPA diagnosis of embolism, the degree of embolism can be further quanti ed. The Qanadli index tends to be de ned according to the location of the embolus and the degree of obstruction, and can better evaluate the effect before and after treatment. This study shows that after treatment in 30 patients, the embolized pulmonary segment was signi cantly reduced, nearly half of the incompletely blocked pulmonary artery emboli disappeared, and part of the completely blocked blood vessel returned to patency, which in turn led to a decrease in PAOI, and a signi cant decrease in the diameters of MPAd, RPAd, and LPAd, indicating that the patient Pulmonary hypertension has been signi cantly improved. Clinically, the diagnosis of RVD mainly depends on echocardiography, cardiac injury markers and the ratio of left and right ventricular diameter of CTPA, and the detection rate of the latter two methods is relatively high [10]. Because of its high diagnostic speci city, CTPA can not only accurately locate the embolus, judge the degree of embolism, but also measure the diameter of left and right cardiac cavities and arteries. Therefore, CTPA is often used to diagnose PE and obtain the signs of RVD. Previous studies have con rmed that when RVd/LVd > 1, it can be used as a standard to judge PE with right ventricular dysfunction [11,12]. Heyer et al. [13] further proposed that RVd/LVd was positively correlated with mortality to a certain extent. Therefore, judging the improvement of RVd / LVd after treatment has important guiding signi cance for the prognosis of patients. In this study, RVD/LVD improved the most after treatment. And research shows that PAOI and RVd/LVd are positively correlated. When PE occurs, pulmonary artery pressure increases, and then right ventricular dilation occurs. At the same time, pulmonary venous return decreases signi cantly, resulting in left ventricular insu ciency. Studies have proposed [14] that there is a close negative correlation between PAOI and atrium parameters, and the short diameter of RV is positively correlated with PAOI. Therefore, dilatation of the right ventricle causes the ventricular septum to be at or even convex to the left ventricle, leading to RVd /LVd increases. This theoretically explains the reason why PAOI is closely related to the RVd/LVd value. This indicates that the larger the range of obstruction, the more severe the obstruction, and the more likely it is to cause right heart dysfunction.
D-dimer is one of cross-linked brin degradation products. When intravascular thrombosis is formed, brin is dissolved to form D-dimer, which is used clinically to re ect the important laboratory index of thrombosis and thrombolytic activity. D-dimer can be detected in the blood about 2 hours after thrombosis, and its half-life is about 8 hours. However, D-dimer is not a speci c marker of coagulation activity: under all processes and conditions that produce and destroy brin again, the value of D-dimer may increase [15]. When D-dimer is normal, PE can be excluded. When D-dimer is raised, it is necessary to diagnose with CTPA [16]. Study has suggested [17] that there is a correlation between the level of D-dimer and the degree of pulmonary artery obstruction. And the increase of D-dimer is related to the increase of short-term and 3-month mortality. In this study, D-dimer changed signi cantly after treatment (P<0.01), and the correlation with PAOI was signi cant. After the patient was treated, the level of D-dimer decreased, the number of emboli decreased or disappeared, and the PAOI value decreased. Study has shown [18] that the level of D-dimer is closely related to the incidence of all types of VTE in COVID-19 patients. Therefore, it is best to perform D-dimer assessment daily to assess the disease progression of severely infected patients. Once the D-dimer level is> 1000 ng/mL, anticoagulation therapy should be started. Van et al. have con rmed that the threshold of D-dimer should be adjusted for patients aged 50 or over (age 10ng/mL) [19].
Brain natriuretic peptide is the secretion of ventricular myocardium after right ventricular dysfunction caused by right ventricular overload and dilation. cTnI is the most sensitive and speci c marker of cardiomyocyte damage. Studies have shown [20,21] that the cTnI level of RVD patients is signi cantly higher than that of patients with normal right heart function, and the increase in cTnI level is a prognostic sign of increased short-term mortality in patients with acute pulmonary embolism. Harrish et al. [22] proposed cTnI has certain value in predicting the 30-day mortality of PE patients. The combination of cTnI and quantitative CT parameters can improve the prediction of adverse clinical outcomes [23]. NT-proBNP is related to the diagnosis of right ventricular dysfunction in PE patients and is an important predictor of all-cause hospitalization or short-term mortality in these patients [24]. NT-proBNP is mainly synthesized and secreted by ventricular myocytes. Changes in ventricular load and ventricular wall tension are the main conditions for increased synthesis and secretion of NT-proBNP. This provides a biological basis for the increase of NT-proBNP during acute pulmonary embolism and RVD. This study found that D-dimer, cTnI, NT-proBNP, LDH, CK had statistically signi cant differences before and after treatment (P<0.05), while the difference in AST was relatively insigni cant. Pulmonary embolism will further lead to right heart insu ciency, leading to an increase in indicators of myocardial injury. Except for D-dimer, there is no obvious correlation between other indicators and PAOI.

Conclusion
Pulmonary embolism has a high incidence rate and mortality. RVD is the main cause of death. CTPA is often used as the gold standard for clinical diagnosis of pulmonary embolism because of its high speci city, good spatial resolution and multiplanar reconstruction capability [25]. It can not only intuitively show embolic obstruction, but also make preliminary assessment of cardiac function. It is of great signi cance to evaluate the therapeutic effect and prognosis. The datasets generated and analysed during the current study are not publicly available due to privacy concern and patient con dentiality but are available from the corresponding author on reasonable request.  Figure 1 a1, a2: CTPA images before and after treatment showed that the right inferior pulmonary artery embolism was lled with contrast agent and the lumen was unobstructed; c1, c2: CTPA images before and after treatment showed that the left inferior pulmonary artery embolism was lled with contrast agent and the lumen was unobstructed; c1, c2: MAPd, AAd before and after treatment, the diameter and pressure of large vessels decreased after treatment; c1, c2:RV/LV were 1.43 and 0.93 before and after treatment, respectively. The ratio after treatment was < 1, and the right ventricular load was reduced.