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The influence factors on the resolution of pulmonary embolism by CT pulmonary angiography

Thrombosis Journal volume 23, Article number: 88 (2025) Cite this article

Abstract

AbstractSection Objective
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Residual chronic obstruction of Pulmonary Embolism (PE) can contribute to pulmonary hypertension and persistent cardiopulmonary limitations. This study comprehensively investigates the influence factors on the resolution of PE clots by CT pulmonary angiography (CTPA).

AbstractSection Methods

A retrospective analysis of 102 patients with acute PE diagnosed by CTPA was conducted based on a registered prospective PE cohort (NCT06073366). Follow-up CTPA studies (3 to 6 months post-diagnosis) were analyzed for the rate of improvement and the complete resolution rate of PE clots. Univariate analyses were performed using chi-square tests, and multivariate logistic regression was applied to adjust for confounding factors.

AbstractSection Results

A total of 2,958 vessels from 102 participants were analyzed, 219 were completely obstructed, and 1439 were partially obstructed. We did not identify any factors that had a significant effect on the rate of improvement. The complete resolution rate of PE clots was lower in completely obstructed vessels compared to partially obstructed vessels, and they had a 110% higher risk of residual thrombus (OR: 2.10, 95% CI: 1.46–2.98, p < 0.001). The rate of complete resolution of PE clot remained lower in accepting thrombolytic than in accepting anticoagulation (OR: 2.01, 95% CI: 1.14–3.77, p < 0.001). However, there was no significant difference in the effect of risk stratification of PE, location of clots (central clots only Vs central and peripheral clots Vs peripheral clots only), elderly, sex, obesity, and comorbid deep venous thrombosis on the complete resolution rate of PE clots.

AbstractSection Conclusion

Patients with completely obstructed PE had a higher risk of residual thrombus than those with partially obstructed through medical therapy. The study highlights that after receiving medical therapy, patients with PE who have complete obstruction could require further exploration of treatment strategies for residual thrombus.

Background

Pulmonary embolism (PE) is a potentially life-threatening disease that occurs when thrombi block one of the pulmonary arteries or its branches [1]. Incidence rates of PE range from 53 to 162 per 100,000 population and rise over time, it may cause about 300,000 deaths per year in the US, ranking high among the causes of cardiovascular mortality [2]. Computed tomography pulmonary angiography (CTPA) is capable of safely excluding the PE population with a relatively low pre-test probability of the disease in a non-invasive way and has an adequate specificity to set the indication for anticoagulant treatment, making it the first choice of diagnosis and follow-up of PE patients [3]. It is recommended to initiate at least three months of anticoagulation treatment for PE patients, treatment can be prolonged in patients based on the underlying cause of PE, though systemic thrombolytic therapy can lead to a significant reduction in the risk of hemodynamic decompensation or collapse, it is paralleled by an increased risk of severe extracranial and intracranial bleeding [4]. Thus, it is only recommended for high-risk PE and intermediate-risk PE with hemodynamic deterioration [5]. Advanced mechanical interventions for acute PE, including surgical pulmonary embolectomy, catheter-directed thrombolysis (CDT), and catheter-based embolectomy, are designed to expeditiously restore pulmonary blood flow, reduce thrombus burden, and stabilize hemodynamic parameters. These approaches are primarily indicated for high-risk (massive) PE with hemodynamic instability and select intermediate-risk (submassive) PE cases with significant right ventricular dysfunction. Despite their efficacy, these interventions are associated with inherent procedural risks and invasiveness. Furthermore, their resource-intensive nature and substantial economic costs pose significant considerations, necessitating careful patient selection and multidisciplinary evaluation to optimize outcomes [6,7,8].

The resolution rates of PE clots evaluated by CTPA reported in the literature are highly variable. Studies with higher proportions of complete resolutions ranged from 68.8 to 91% within the time range of 28 days to 4.5 months, and studies with lower proportions of complete resolutions ranged from 32 to 44% within the time range of 21 to 42 days [9,10,11,12,13,14]. A latest prospective study revealed that the overall estimated probability of complete resolution was 42% at 7 days, 56% at 10 days, and 71% at 45 days [15]. Residual chronic obstruction of PE can contribute to persistent cardiopulmonary limitations and pulmonary hypertention. To the best of our knowledge, prior research has not yet comprehensively examined the variables that impact the rate of resolution [16], therefore, we aim to comprehensively compare the influence factors on the revascularization and resolution rate of PE following at least three months of medical therapy.

Materials and methods

The study was approved by the Institutional Review Board. Written informed consent was obtained from all patients included. All clinical data and imaging were de-identified before analysis.

Study population

Based on a registered prospective PE cohort research (NCT06073366), from October 2014 to April 2020, 674 patients were consecutively recruited in the Chinese Academy of Medical Sciences Fuwai Hospital. The inclusion criteria were acute PE patients diagnosed by CTPA and had at least one follow-up CTPA in the interval of 3 to 6 months after diagnosis. All participants should accept anticoagulation treatment before finishing follow-up CTAP. A total of 102 individuals who underwent at least one follow-up CTPA within the designated period were included. The selection criteria for the follow-up CTPA study in patients with more than one was as follows: we selected the earliest available CTPA follow-up study with a complete resolution or the last follow-up CTPA study with a partial resolution for analysis purposes.

CTPA imaging protocol

All patients were examined with a second-generation Dual Source CT scanner (Somatom Definition Flash, Siemens Healthcare, Forchheim, Germany). For contrast medium enhancement CT was performed using axial acquisition, and scanning ranged from the thoracic entrance to the diaphragm level. The CT scan was triggered using the bolus-tracking technique: the region of interest was placed on the pulmonary trunk, and image acquisition was started 3 s after attenuation had reached a predefined threshold of 80 HU. CT parameters were used as below: detector collimation 64 × 0.6 mm, gantry rotation time 0. 33 s, pitch 0. 6; tube voltage of 100 kV and tuber current determined by Care Dose 4D (Siemens), range from 113 to 394 mAs, depending on patient size, Tube current modulation was used to minimize radiation. Images were reconstructed with a slice thickness of 0. 75 mm. Contrast medium (Iopromide 370 mg/ml; Bayers-Schering Pharma, Germany) with a total volume of 50–60 ml was injected at a flow rate of 5 ml/s administered via 20-gauge trocar in the antecubital vein using a power injector (Stellant; Medrad, Indianola, Pennsylvania).

Image analysis

Images from the baseline and follow-up CTPA investigations that had been de-identified were moved to a PC workstation. Two radiologists with over six years of body imaging expertise randomly examined the imaging studies. All patient information was concealed from the radiologists. The senior investigator, who possesses over 12 years of expertise, arbitrated any disagreement that arose between the two readers while maintaining anonymity regarding the CTPA, patient characteristics, and the origin of the disagreement.

Qanadli scoring systems were employed in semiquantitative thrombotic load measurements to ascertain the extent of vascular obstruction. A normal vessel was scored at 0, a partially obstructed vessel at 1, and a completely obstructed vessel at 2 [17]. Improvement was defined as any improvement over baseline in the follow-up CT scan (measured as a lower Qanadli score than previously). The complete resolution of a PE clot was measured by Qanadli score decreased to 0. Recurrence was defined as an increase in PE obstruction degree (measured as a higher Qanadli score than before).

The analysis included 29 pulmonary arteries total from each patient: 11 central pulmonary arteries (main pulmonary artery, right and left pulmonary arteries, right and left interlobar arteries, and 6 lobar arteries) and 18 peripheral pulmonary arteries (segmental pulmonary arteries).

Statistical analysis

R statistical software (version 4.1.2, http://www.r-project.org) and SPSS statistical software (version 26.0) were used for data analysis. We targeted the obstructed vessel rather than the patient to investigate the effect of the degree of vessel obstruction on the medical therapy of PE. Obstructed vessels were divided into two groups, partially obstructed vessels (Qanadli score = 1) and completely obstructed vessels (Qanadli score = 2), with outcomes of revascularization and resolution, and factors that the investigators thought might affect thrombus resolution were included. The position of clots was divided into 3 group: (1) vessels with central clots only; (2) vessels with central and peripheral clots; (3) vessels with peripheral clots only. Quantitative data with normal distribution is defined as mean ± standard deviation, with skewed distributions as median [25th, 75th percentiles]. Categorical data is defined as n (%). Chi-square analysis was used to testify to the difference in included factors between the two groups. Corrected chi-square test results were used when at least one theoretical frequency ≥ 1 while ≤ 5. Fisher’s exact probability method is used when at least one theoretical frequency < 1. Factors with significant differences in the chi-square analysis were included in the logistic regression for multivariate analysis to correct for the effects of confounding factors.

Results

The flowchart of patient inclusion is shown in Fig. 1, and the baseline characteristics of the included patients are shown in Table 1. A total of 2,958 vessels from 102 participants were analyzed, of which 1296 were normal, 4 experienced recurrences, 1439 were partially obstructed, and 219 were completely obstructed.

Fig. 1
figure 1

Flowchart of patient inclusion

Full size image
Table 1 Variables of demographic characteristics, imaging and clinical information of the patients at the time of diagnosis
Full size table

The rate of improvement

Univariate analysis of included factors at a significance level of 0.05 was performed, the rates of improvement were lower in vessels receiving thrombolytic therapy than in those receiving anticoagulation therapy (p < 0.001), in vessels with central and peripheral clots than in those vessels with peripheral clot only (p = 0.029), and in vessels with medium-to-high risk PE than in those with low-risk PE (p < 0.001). However, there was no statistically significant difference in the rate of improvement between partially obstructed vessels and completely obstructed vessels, between male and female participants, between elderly (≥ 65 years) and younger (≥ 65 years) participants, between participants with and those without DVT participants, and between participants who were obese (≥ 28) and those who were not obese participants.

After performing a multivariate analysis, we found that the rate of improvement in partially obstructed vessels remained not significantly different from that in completely obstructed vessels (p = 0.297). The effect of PE risk stratification (low risk versus intermediate-to-high risk), position of clots (central and peripheral clots versus peripheral clots only), and treatment strategies (anticoagulation alone versus anticoagulation and thrombolytic therapy) on the rate of improvement was no longer significantly different. We did not identify any factors that had a significant effect on the rate of improvement. The improvement rate results are shown in Table 2.

Table 2 Results of improvement rate of PE clots
Full size table

The rate of complete resolution

Univariate analysis of included factors at a significance level of 0.05 was performed, the results showed that completely obstructed vessels (p < 0.001), vessels with central and peripheral clots (p = 0.012), receiving thrombolytic (p < 0.001) and medium-to-high risk PE (p < 0.001) were significantly associated with lower rates of complete resolution. However, there was no significant difference in the effect of elderly, sex, obesity, and comorbid DVT on the resolution rate of PE clots.

In multivariate analysis, the rate of complete resolution of PE clot remained lower in completely obstructed vessels than in partially obstructed vessels, and completely obstructed vessels had a 110% higher risk of residual thrombus (OR: 2.10, 95% CI: 1.46–2.98, p < 0.001). The rate of complete resolution of PE clot remained lower in receiving thrombolytic than in receiving anticoagulation (OR: 2.01, 95% CI: 1.14–3.77, p < 0.001). However, position of clots and PE risk stratification were no longer significantly associated with the resolution rate. The results of the resolution rate are shown in Table 3.

Table 3 Results of complete resolution rate of PE clots
Full size table

Discussion

In this article, we aim to comprehensively investigate the impact factors on the rate of improvement and complete resolution of PE clots in patients following at least three months of medical therapy (anticoagulation alone or anticoagulation and thrombolytic). To the best of our knowledge, however, prior research has not yet comprehensively examined the variables that impact the resolution of clots; for instance, previous relevant studies did not include the obstruction degree of the convicted vessel and medical treatment strategies. The resolution rate between completely obstructed and partially obstructed vessels may differ after medical therapy due to the area of drug exposure, position, and so on. Compared to anticoagulants, thrombolytic medicines may revascularize vessels more quickly, resulting in early complete resolution of clots. It is the first study to investigate the degree of obstruction and treatment strategies on the resolution of PE clots. We recruited patients from a registered prospective PE cohort and set a follow-up period of three to six months, the CTPA data obtained over this period can clearly show the effect of medical therapy, allowing us to investigate the associated contributing factors.

Following an acute PE, there can be a range of outcomes, from full resolution of symptoms with complete restoration of normal perfusion to residual chronic obstruction that contributes to pulmonary hypertension (PH) and persistent cardiopulmonary limitations [18]. The current rate of complete thrombus resolution has been reported by various studies, with most studies reporting complete thrombus resolution in 68.8% − 91% of patients after three months of anticoagulation [9,10,11, 14, 15]. However, two studies reported lower rates of complete resolution (32% and 44%) [12, 13]. Several pathophysiological alterations are brought about by residual thrombus, these chronic obstructions become organized and fibrotic and, together with the concomitant remodeling of the pulmonary vasculature, which can result in progressive PH, also known as chronic thromboembolic pulmonary hypertension (CTEPH), right heart failure, and even mortality. Although the actual frequency of CTEPH is unclear, it is estimated to be approximately 3% after acute PE [19,20,21]. Meanwhile, on the spectrum of potential outcomes following PE, chronic thromboembolic pulmonary disease (CTEPD) without PH is becoming a more widely recognized entity. It is characterized by the existence of persistent perfusion abnormalities with associated symptoms but no resting PH [22].

The degree of obstruction was one of the important factors we were concerned with, and the results showed that the rate of improvement did not significantly differ between partially and completely obstructed vessels. After receiving medical therapy, 11.90 per cent of partially obstructed vessels and 11.40 per cent of completely obstructed vessels did not show improvement from the pre-treatment period, which suggests that the ineffective rate of medical therapy was similar in both groups (p = 0.934). After multivariate correction, the rates of no improvement between the two groups still showed no significant difference (p = 0.297).

The rate of complete resolution of PE clot was significantly lower in vessels with complete obstruction than in vessels with partial obstruction. After correcting two covariates that were significant in single-factor analysis (treatment strategy and PE risk stratification), we found that the rate of complete resolution of PE clot remained lower in completely obstructed vessels than in partially obstructed vessels, and they had a 110% higher risk of residual thrombus (OR: 2.10, 95% CI: 1.46–2.98, p < 0.001) . It might be that completely obstructed vessels had a larger thrombus burden and a smaller area of medication exposure. Due to the larger contact zones in partially obstructed vessels, where the thrombus has not completely closed the channel and blood can still pass through, drugs may be able to reach the thrombus and function more effectively.

There is an ongoing debate over the clot resolution rate of peripheral pulmonary arteries versus central pulmonary arteries. Higher rates of clot resolution have been reported in peripheral pulmonary arteries by Aghayev et al. and Ak et al. [11, 15] In contrast, Stein et al. reported a lower rate of clot resolution in peripheral pulmonary arteries [9]. Our research indicates that vessels with peripheral clots alone exhibited a higher resolution rate than those with both central and peripheral clots, however, this difference did not reach statistical significance. Additionally, patients treated with thrombolytic therapy had a lower improvement and resolution rate than patients treated with anticoagulation. This could be because patients receiving thrombolytic therapy had a higher risk classification for PE and heavier thrombus load.

Medical therapy is the cornerstone of PE treatment, and there are no clear recommendations for treating patients with residual thrombus after medical therapy [5, 23]. Mechanical treatment can quickly clear the clots, relieve right ventricular dysfunction and restore hemodynamics. Both surgical (pulmonary embolectomy) and interventional (catheter-directed thrombolysis and catheter-based embolectomy) treatments for acute pulmonary embolism have progressed considerably, with high efficiency and safety rates [6, 7]. The risk of residual thrombus was higher in completely obstructed vessels, and there is still a certain possibility that medical therapy alone will not be enough to resolve the PE clot completely. Chronic obstruction of the vessel can lead to a higher risk of CTEPH and cardiopulmonary limitation. Removal of residual thrombus by surgical or interventional methods can result in significant symptomatic relief and hemodynamic improvement [4]. There exists a need for further exploration of treatment strategies for residual thrombus except medical therapy to avoid deterioration of the condition.

Our study has several limitations: First, our study was a retrospective analysis and included a relatively small number of patients; Second, there was a heterogeneity between patients receiving anticoagulation and those receiving thrombolytic therapy, which may have had an impact on the results of the analysis.

Conclusion

Patients with completely obstructed PE had a higher risk of residual thrombus than those with partially obstructed through medical therapy. There is still a certain possibility that medical therapy alone will not be enough to resolve the PE clot completely. The study highlights that after receiving medical therapy, patients with PE who have complete obstruction could require further exploration of treatment strategies for residual thrombus.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

PE:

Pulmonary embolism

DVT:

Deep vein thrombosis

CETPD:

Chronic thromboembolic pulmonary disease

PH:

Pulmonary hypertension

CTEPH:

Chronic thromboembolic pulmonary hypertension

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Funding

The study was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-040) and the National Clinical Research Center of Cardiovascular Diseases, Shenzhen, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (NCRCSZ-2023-015).

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Author notes

  1. Zhiqiang Liu and Yuanrui Deng contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Zhiqiang Liu, Yuanrui Deng, Yan Wu, Xin Gao, Lingtao Chong, Lu Hua & Tingting Guo

  2. Department of Radiology, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Weihua Yin

  3. Department of Epidemiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Jingyu Wang

  4. Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China

    Lu Hua

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  1. Zhiqiang Liu
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Contributions

Design of the study: L Hua and TT Guo; Data collection: Y Wu, X Gao, WH Yin and LT Chong; Data analysis: ZQ Liu, YR Deng, and JY Wang; Manuscript drafting: ZQ Liu and YR Deng; Revision: L Hua and TT Guo.

Corresponding authors

Correspondence to Lu Hua or Tingting Guo.

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The study was approved by the Institutional Review Board. Written informed consent was obtained from all patients included. All clinical data and imaging were de-identified before analysis.

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The authors declare no competing interests.

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Liu, Z., Deng, Y., Wu, Y. et al. The influence factors on the resolution of pulmonary embolism by CT pulmonary angiography. Thrombosis J 23, 88 (2025). https://doi.org/10.1186/s12959-025-00773-1

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Thrombosis Journal

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