Residual pulmonary thromboemboli after acute pulmonary embolism

doi:10.1016/j.ejim.2011.08.018

European Journal of Internal Medicine

Volume 23, Issue 4, June 2012, Pages 379-383

https://doi.org/10.1016/j.ejim.2011.08.018 Get rights and content

Abstract

Background

After an acute pulmonary embolism (PE), the complete resolution of thromboemboli may not be routinely achieved. The rate of persistence may depend on the time and the diagnostic technique used for evaluation.

Patients and methods

Patients were diagnosed with acute PE by means of computed tomography angiography (CTA). While they were receiving anticoagulant therapy, a second CTA was used to explore the rate of persistence of residual thromboemboli. During the initial episode, the plasma levels of Troponin I and natriuretic peptide, patient demographics, and hemodynamic and gas exchange data were evaluated as risk factors for persistence of pulmonary thromboemboli.

Results

In this study 166 patients were diagnosed. A second CTA was not made in 46 (28%) patients for different reasons. In 120 (72%) patients a second CTA was made 4.5 [SD2.34] months after the initial episode (range 2–12 months). Complete clearance of thrombi occurred in 89 (74%, 95% CI 65–81) patients. Residual thrombi remained in 31 (26%, 95% CI 18–34) patients. In 6%, 13% and 81% of the patients the size of the residual thrombi was greater, similar to and smaller than initially diagnosed, respectively.

The risk factors for residual thrombi included the thrombotic burden (OR 1.95), the alveolar to arterial difference of oxygen (OR 1.64), and the clinical antecedents of venous thromboembolic disease (OR 0.65).

Conclusions

After 4.5 months of anticoagulant therapy, residual pulmonary thromboemboli persisted in 26% of the patients. The risk factors for residual thromboemboli include a greater initial thrombotic burden, a deeper gas exchange disturbation and a history of previous venous thromboembolism.

Introduction

Traditionally the study of normalized pulmonary perfusion after an acute pulmonary embolism has been evaluated in prospective studies using lung scintigraphy. These studies demonstrated that pulmonary circulation normalized in 34–43% of patients at a variable times, ranging between 3 and 6 months after the acute episode [1], [2].

Currently, pulmonary circulation can be evaluated with helical computed tomography [3] (CT), and a few studies have addressed the subject of repermeabilization after an acute occlusion of the pulmonary arterial tree. In a study with 62 consecutive patients, after a mean of 11 months after the acute episode, a follow-up CT scan was performed. Complete resolution of pulmonary thrombi was found in 48% of patients [4]. In another study with 19 consecutive patients, helical CT was used to check the evolution of thrombi 6 weeks after an acute pulmonary embolism, and a resolution rate of 32% was observed [5].

A systematic analysis of studies [6] evaluating pulmonary reperfusion, some of them with scintigraphy and others with helical CT scan, revealed that a complete resolution of pulmonary embolism is not routinely achieved, and that depending on the time of evaluation, more than 50% of patients show persistent perfusion defects in pulmonary circulation 6 months after an acute pulmonary embolism. However, the number of patients included in these studies has been small, particularly in studies using CT angiography (CTA).

Patients with acute pulmonary embolism are at risk for recurrent venous thromboembolic events [7], [8]. The rate of relapsing pulmonary embolism can be as high as 10% after a discontinuation of anticoagulant therapy, particularly in cases of unprovoked pulmonary embolism, and the clinical presentation can be nonspecific; thus, it can be difficult to determine whether new defects of perfusion are actually new or whether these defects are thrombi from a previous pulmonary embolism. For this reason, studying the repermeabilisation of the pulmonary arterial tree can be useful. Thus, we studied consecutive patients with a second CTA and analyzed the possible factors that are associated with the persistence of thrombi in the pulmonary arterial tree.

Section snippets

Patients and methods

To evaluate the rate of vascular repermeabilization after an acute pulmonary embolism, all consecutive patients diagnosed with acute pulmonary embolism using CTA were admitted to an area of internal medicine that included 12 beds to diagnose and treat patients. After their discharge, the patients were evaluated in the polyclinic as outpatients with a second CTA. The aim was to observe the disappearance or the persistence of thromboemboli in the pulmonary arterial tree.

Results

Overall, during a period of 5 years from January 2006 to December 2010, 166 patients (male 85 [51%]) were admitted with a diagnosis of acute pulmonary embolism made by mean of CTA, with a median age of 74 [IQR 17] years.

In 46 (28%) patients (male 25 [54%]), a second CTA could not be performed for different reasons (Table 1). The mean age of these patients was 75 [SD 12] years old, (p < .001 with respect to patients with repeated second CTA).

A second CTA was obtained in 120 (72%) patients with a

Discussion

The development of multidetector CT [3] has enabled the facile visualization of pulmonary arteries up to subsegmental levels. An additional advantage is that it allows the evaluation of other intra-thoracic structures, the existence of lung infarction, the relationship of right to left ventricle as a sign of right ventricular overload [10] and the coexistence of other pathological processes with relatively few deleterious effects.

Studies made with lung scintigraphy have demonstrated that

Learning points

•
In the setting of acute pulmonary embolism, the initial thrombotic burden, the deeper gas exchange alteration and a previous history of venous thromboembolism predict the persistence of thrombotic material in pulmonary arteries.
•
Mapping pulmonary arteries is important in order to determine the etiology of new episodes of dyspnea in patients with clinical antecedents of pulmonary embolism.
•
The sort and the length of antithrombotic therapy could be influenced by the persistence of pulmonary

Conflict of interest

This manuscript is the result of independent investigation and authors has not any conflict of interest.

Acknowledgment

We thank Professor Miguel Andériz for his invaluable advice and review of statistical methods.

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CTEPH: A Kaiser Permanente Northern California Experience
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Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening form of pulmonary hypertension and the only potentially curable form of the World Health Organization Pulmonary Hypertension classes. Thus, the prompt and accurate diagnosis of this condition is imperative. Despite widespread chronic symptoms following acute pulmonary embolism (PE), the condition is rarely considered, and an externally validated inexpensive diagnostic algorithm is lacking.
A long-term, retrospective cohort study was conducted to assess the incidence of CTEPH following acute PE in a real-world study population. Additional data were collected regarding the practice patterns of diagnostic testing and imaging, particularly in patients with persistent or recurrent symptoms. Amongst diagnosed CTEPH patients, previously established risk factors were evaluated for degree of risk and commonly used diagnostic tests (electrocardiogram [ECG] right ventricular hypertrophy [RVH] pattern, B-type natriuretic peptide [BNP] elevations) employed during this period were evaluated and assessed for feasibility as screening tests. The study population was obtained from the MAPLE study cohort, comprised of patients presenting with acute PE in 21 community medical centers across the Kaiser Permanente Northern California system from January 2013 to April 2015. Diagnosis of CTEPH was confirmed via pulmonary vascular imaging (ventilation/perfusion [V/Q] scanning, computed tomography angiography, pulmonary angiography) and diagnostic right heart catheterization (RHC). Probable diagnoses were defined as a combination of suggestive echocardiographic and RHC findings. Additional inclusion criteria included age (≥18 years) with at least 2 years follow up and no previous diagnosis of CTEPH or PE during the prior 30 days.
There were 1973 patients who met inclusion criteria (mean age 62.4 years). Despite 75 % of patients developing symptoms consistent with CTEPH >3 months following acute PE, only 5.6 % of these symptomatic patients underwent V/Q scanning. There was overall a very low cumulative incidence of CTEPH (2.3 %), which was significantly higher amongst patients with symptoms compared to those without symptoms. When controlled for confounding in the multivariate analysis, only recurrent PE (HR 19.3, P < 0.001) and pulmonary artery systolic pressure >50 mmHg (HR 10.4, P < 0.001) were statistically significant predictors of CTEPH. Of the non-invasive diagnostic tests, ECG criteria for RVH were found to be poorly sensitive (2.6 %), but very specific (98.8 %) for CTEPH. Elevated levels of BNP alone were more sensitive than RVH ECG criteria (76.3 %) but poorly specific (44.4 %).
The diagnosis of CTEPH is uncommonly made following acute PE. Despite the frequency of persistent symptoms consistent with CTEPH following acute PE, the appropriate diagnostic work-up is rarely undertaken as evidenced in this cohort. This suggests that CTEPH is underappreciated and rarely considered, likely underestimating the true incidence in this cohort. Future studies are needed to elucidate the true prevalence of CTEPH and further investigate both the optimal diagnostic tools and timing of appropriate screening. These discoveries may help guide future development of diagnostic algorithms that can effectively rule out and accurately identify this potentially curable disease in a timely manner.
The Resolution Rate of Pulmonary Embolism on CT Pulmonary Angiography: a Prospective Study
2022, European Journal of Radiology
Citation Excerpt :
Although we found an association between higher thrombotic burden measured with indirect methods were associated with slower resolution rates in univariable analysis, they were not independently associated in multivariable analysis. However, a recent study showed that higher initial clot burden assessed by Qanadli scoring system, is an independent risk factor for residual clot [10]. Semiquantitative scoring systems are also yielded predictions for short-term mortality, with most [22–27] but not all studies [28,29] showing a lack of correlation.
To prospectively assess the rate of clot resolution from CT pulmonary angiography (CTPA) in patients with acute pulmonary embolism (PE).
This prospective cohort study included 290 patients (136 men, 154 women; mean age, 51.9 years) with acute PE. All patients had a CTPA at the presentation and had at least one follow-up within 6 months (mean 72.7 days). Sixty-four percent of patients had follow-up scans for research purposes within a pre-determined period (between 28 and 184 days; mean, 78.27 days) and 36 % had (between 2 and 184 days; mean, 62.78 days) for a clinical indication. The volume of each clot was measured using a semi-automated quantification program. The resolution rate was evaluated by interval-censored analysis.
The overall estimated probability of complete resolution was 42 % at 7 days, 56 % at 10 days, and 71 % at 45 days. Achieving complete resolution was significantly faster in patients with peripheral clots (HR: 1.78; CI: 1.05–3.03, p = 0.032) but slower in patients with consolidation and history of venous thromboembolism (VTE), (HR: 0.37; CI: 0.18–0.79, p = 0.01 and HR: 0.57; CI: 0.35–0.91, p = 0.019, respectively). Although the patients with cancer showed a faster resolution rate (HR: 1.67; CI: 1.05–2.68, p = 0.032), the mortality rate was significantly higher than non-cancer patients.
The resolution rate of clot burden in acute PE was associated with patients' clinical presentation variables and CTPA imaging biomarkers. This information may be incorporated into designing a prediction rule and determining the appropriate duration of anticoagulation therapy in patients with acute PE.
Risk factors for chronic thromboemboli after pulmonary thromboembolism
2022, European Journal of Internal Medicine
Pulmonary and cardiac variables associated with persistent dyspnea after pulmonary embolism
2021, Thrombosis Research
Citation Excerpt :
All of these alterations may cause impaired gas diffusion capacity resulting in a reduced DLCO. Residual perfusion defects were detected in 22% of the participants in our cohort, which compares well with a range of 20–50% reported in previous studies [32–36]. Perfusion defects have in other studies been linked to dyspnea and functional limitations [34], and often the term chronic thromboembolic pulmonary disease (CTEPD) is used [37].
Persistent dyspnea is common in follow-up after pulmonary embolism (PE), but the underlying mechanisms are poorly understood.
This cross-sectional study included subjects aged 18–75 years with confirmed PE by computed tomography pulmonary angiography (CTPA) 6–72 months earlier. A total of 180 participants underwent clinical examination, incremental shuttle walk test, laboratory tests, transthoracic echocardiography, pulmonary function tests and ventilation/perfusion scintigraphy. In further analysis, we divided participants into two groups; “dyspnea” or “no dyspnea”, based on interview and questionnaires at inclusion. The association of cardiac and pulmonary variables with persistent dyspnea was assessed using multiple logistic regression analysis.
In total, 44% (95% CI: 39%–51%) of the participants reported persistent dyspnea after PE. Age (adjusted odds ratio (aOR) 0.93 per year, 95% CI: 0.90–0.97, P = 0.001), body mass index (BMI) (aOR 1.14 per kg/m², 95% CI: 1.04–1.25, P = 0.004), recurrent venous thromboembolism (VTE) (aOR 3.69, 95% CI: 1.45–9.38, P = 0.006) and diffusion capacity of the lung for carbon monoxide (DLCO) (aOR 0.95 per increase of 1%, 95% CI: 0.92–0.98, P = 0.001) were independently associated with persistent dyspnea.
Persistent dyspnea was prevalent after PE. Age, BMI and recurrent VTE were independently associated with dyspnea. Apart from reduced DLCO, no other cardiac or pulmonary variables were associated with persistent dyspnea.
Chronic Thromboembolic Disease and Chronic Thromboembolic Pulmonary Hypertension
2021, Clinics in Chest Medicine
Predictors of Recovery in Patients Supported With Venoarterial Extracorporeal Membrane Oxygenation for Acute Massive Pulmonary Embolism
2020, Annals of Thoracic Surgery
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has emerged as a promising initial support strategy for acute massive pulmonary embolism. However, it remains unclear which patients will ultimately require surgical pulmonary embolectomy (SPE) vs anticoagulation alone.
All consecutive patients (2015-2018) with confirmed massive PE, placed on VA-ECMO utilizing a protocolized approach, were reviewed. Per protocol, patients were supported for 3 to 5 days before reevaluation of right ventricular (RV) function via echocardiography. If RV function recovered, VA-ECMO was discontinued with no further intervention (no-SPE group). In patients with persistent RV dysfunction, SPE was performed.
Forty-five patients were identified, and 41 patients were treated per protocol. Seventy-three percent responded to anticoagulation alone, and 27% required SPE. Factors associated with SPE rather than decannulation with anticoagulation alone included prolonged shortness of breath, elevated N-terminal prohormone of brain natriuretic peptide, enlarged pulmonary artery diameter, and history of venous thromboembolism. A predictive algorithm was developed with a negative predictive value of 97% and a specificity of 97% for a low-risk score, and a positive predictive value of 100% and sensitivity of 67% for a high-risk score. Overall, 90-day survival was 97% in the no-SPE group and 100% in the SPE group.
In this cohort, greater than 70% of patients who presented with massive PE and supported with VA-ECMO ultimately recovered with anticoagulation alone. Specific risk factors, likely related to thrombus chronicity, may be associated with lack of RV recovery, and can be utilized for consideration of early surgical intervention to minimize VA-ECMO duration.

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Original articleResidual pulmonary thromboemboli after acute pulmonary embolism

Abstract

Background

Patients and methods

Results

Conclusions

Introduction

Section snippets

Patients and methods

Results

Discussion

Learning points

Conflict of interest

Acknowledgment

Chest

Chest

Eur J Intern Med

Am J Med Sci

Chest

Med Clin (Barc)

Scintigraphic control of pulmonary embolism

Eur J Nucl Med

Incomplete recovery of lung perfusion after 3 months in patients with acute pulmonary embolism treated with antithrombotic agents. THESEE Study Group. Tinzaparin ou Heparin Standard: Evaluation dans l'Embolie Pulmonaire Study

J Nucl Med

Multislice computed tomography for pulmonary embolism. A technical marvel

N Engl J Med

Acute central thromboembolic disease: postherapeutic follow-up with spiral CT angiography

Radiology

Spiral CT appearance of resolving clots at 6 week follow-up after acute pulmonary embolism

J Comput Assist Tomogr

Acute pulmonary embolism

N Engl J Med

Patient outcomes after acute pulmonary embolism

Am J Respir Crit Care Med

Original article
Residual pulmonary thromboemboli after acute pulmonary embolism