Usefulness of standard computed tomography pulmonary angiography performed for acute pulmonary embolism for identification of chronic thromboembolic pulmonary hypertension: results of the InShape III study

doi:10.1016/j.healun.2019.03.003

The Journal of Heart and Lung Transplantation

Volume 38, Issue 7, July 2019, Pages 731-738

https://doi.org/10.1016/j.healun.2019.03.003 Get rights and content

BACKGROUND

Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed after a long delay, even though signs may already be present on the computed tomography pulmonary angiogram (CTPA) used to diagnose a preceding acute pulmonary embolism (PE). In this setting of suspected acute PE, we evaluated the diagnostic accuracy of dedicated CTPA reading for the diagnosis of already existing CTEPH.

METHODS

Three blinded expert radiologists scored radiologic signs of CTEPH on initial CTPA scans with confirmed acute PE in 50 patients who were subsequently diagnosed with CTEPH during follow-up (cases), and in 50 patients in whom sequential echocardiograms performed >2 years after the acute PE diagnosis did not show any signs of pulmonary hypertension (controls). All 50 control index CTPA scans had signs of right ventricular (RV) overload. Sensitivity and specificity of expert CTPA reading was calculated, and best-predicting radiologic parameters were identified.

RESULTS

The overall expert reading yielded a sensitivity of 72% (95% confidence interval [CI] 58%–84%) and a specificity of 94% (95% CI 83%–99%) for CTEPH diagnosis. Multivariate analysis identified 6 radiologic parameters as independent predictors: intravascular webs; pulmonary artery retraction or dilatation; bronchial artery dilatation; right ventricular (RV) hypertrophy; and interventricular septum flattening. The presence of 3 or more these parameters was associated with a sensitivity of 70% (95% CI 55%–82%), a specificity of 96% (95% CI 86%–100%), and a c-statistic of 0.92.

CONCLUSIONS

Standardized reading of CTPA scans performed for acute PE can be useful for the diagnosis of CTEPH when structured identification of 6 characteristics is employed during interpretation. The use of this strategy may help reduce diagnostic delay of CTEPH.

Section snippets

Study population

Patient selection for the InShape III study occurred post hoc from the local patient registry of the Vrije University Medical Center (VUmc) (cases) and previous prospective studies (controls).10, 17, 18 Assessment of CTPA scans was performed prospectively. The cases consisted of 50 consecutive patients who were referred to the VUmc, Amsterdam, in the period between 2014 and 2016 for treatment of CTEPH, and had a prior diagnosis of acute PE. The CTEPH diagnosis was confirmed by right heart

Patients

Patients’ characteristics at the time of initial CTPA scan for PE diagnosis are presented in Table 1. Mean age at the time of PE diagnosis was 61 ± 15 years in cases and 56 ± 15 years in controls. A total of 43 (86%) cases had an unprovoked acute PE event and 20 (40%) had recurrent venous thromboembolism (VTE). In the control cohort, these numbers were 29 (58%) and 10 (20%), respectively, for ORs of 5.2 (95% CI 2.0–14) and 2.7 (95% CI 1.1–6.5), respectively. Symptom onset was >2 weeks before PE

Discussion

In this study we have demonstrated that expert radiologists were able to identify 36 of 50 patients with acute PE who were later diagnosed with CTEPH, and correctly excluded CTEPH in 47 of 50 patients from those who did not develop CTEPH after at least 2 years of follow-up, based on close reading of the CTPA scan performed for the initial PE diagnosis. The interobserver agreement between the 3 expert radiologists for the majority of the best predictive radiologic parameters was good. The

Disclosure statement

The authors have no conflicts of interest to disclose. This study was supported by an unrestricted grant from Merck Sharp & Dohme and by a grant from the Dutch Heart Foundation (2017T064 to F.A.K. and G.J.A.M.B.).

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Update in the management of chronic thrombo-embolic pulmonary hypertension
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La hipertensión pulmonar tromboembólica crónica (HPTEC) es una forma potencialmente curable de hipertensión pulmonar (HP) que aparece hasta en 3% de los pacientes tras una embolia pulmonar (EP). En estos pacientes, la EP no se resuelve, dando paso a coágulos fibróticos organizados, con el desarrollo de HP precapilar debido a la obstrucción proximal de las arterias pulmonares. También puede desarrollarse una microvasculopatía distal que contribuye al aumento de la resistencia vascular pulmonar (RVP). La ecocardiografía transtorácica (ETT) es la exploración que permite establecer la sospecha de HP. La gammagrafía pulmonar de ventilación-perfusión (V/Q) es la herramienta fundamental en el estudio de los pacientes con sospecha de HPTEC; si es normal, prácticamente la descarta. El cateterismo cardiaco derecho es obligatorio para el diagnóstico. La HPTEC se define como la existencia de síntomas, defectos de perfusión residuales e HP precapilar tras un periodo mínimo de tres meses de anticoagulación. La angiografía pulmonar ayuda a determinar la extensión y la accesibilidad quirúrgica de las lesiones tromboembólicas. Las personas con HPTEC son candidatas a anticoagulación indefinida. La endarterectomía pulmonar es el tratamiento de elección, resultando en una mejoría clínica y hemodinámica significativa. Aproximadamente un 25% de los pacientes presentan HP residual postendarterectomía. La angioplastia pulmonar con balón (APB) es una técnica endovascular dirigida a lesiones más distales, de utilidad para sujetos con HPTEC inoperable o HP persistente/recidivante postendarterectomía. Ambos tipos de pacientes también se pueden beneficiar de tratamiento farmacológico para la HP. Las tres terapias constituyen los pilares de la terapia, que ha evolucionado hacia un enfoque multimodal.
Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a potentially curable form of pulmonary hypertension (PH) that develops in up to 3% of patients after pulmonary embolism (PE). In these patients, PE does not resolve, leading to organized fibrotic clots, with the development of precapillary PH as a result of the proximal obstruction of the pulmonary arteries. In addition, a distal microvasculopathy may also develop, contributing to the increase of pulmonary vascular resistance. Transthoracic echocardiography is the diagnostic tool that allows to establish the suspicion of PH. Ventilation-perfusion lung scintigraphy is the fundamental tool in the study of patients with suspected CTEPH; if it is normal, virtually rules out the diagnosis. Right heart catheterization is mandatory for the diagnosis of these patients. CTEPH is defined as the existence of symptoms, residual perfusion defects and precapillary PH after a minimum period of three months of anticoagulation. Pulmonary angiography helps determine the extent and surgical accessibility of thromboembolic lesions. CTEPH patients are candidates for long-term anticoagulation. Pulmonary endarterectomy is the treatment of choice, resulting in significant clinical and hemodynamic improvement. About 25% of patients have residual PH post-endarterectomy. Balloon pulmonary angioplasty is an endovascular technique that targets more distal lesions, being potentially useful for patients with inoperable CTEPH or persistent/recurrent PH post-endarterectomy. Both types of patients may also benefit from pharmacological treatment for PH. These three therapies are the cornerstone of CTEPH treatment, which has evolved towards a multimodal approach.
Prevalence and predictors of chronic thromboembolic pulmonary hypertension following severe forms of acute pulmonary embolism
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The true prevalence of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) in the Portuguese population remains unknown. We aimed to assess the prevalence and predictors of CTEPH two years after a symptomatic high- (HR) or intermediate-high risk (IHR) PE.
We conducted a retrospective cohort study of patients admitted with PE between 2014 and 2019 to a Portuguese referral center for pulmonary hypertension.
In this single-center registry of 969 patients admitted with PE (annual incidence of 46/100 000 population), 194 had HR (5.4%) and IHR (14.7%) PE. After excluding patients who died or had no follow-up in the first three months, 129 patients were included in the analysis. The overall prevalence of suspected CTEPH by clinical assessment, Doppler echocardiography and V/Q lung scan was 6.2% (eight patients). CTEPH was confirmed by right heart catheterization in four of these (3.1%). Increased pulmonary artery systolic pressure (PASP) at admission (OR 1.12; 95% CI 1.04–1.22; p=0.005) and the presence of varicose veins in the lower limbs (OR 7.47; 95% CI 1.53–36.41; p=0.013) were predictors of CTEPH. PASP >60 mmHg at admission identified patients with CTEPH at follow-up with sensitivity and specificity of 83.3% and 76.3%, respectively. All patients diagnosed with CTEPH had at least two radiological findings suggestive of CTEPH at the index event.
In our cohort, the prevalence of CTEPH in survivors of severe forms of acute PE was 6.2%. PASP above 60 mmHg and supporting radiological findings on the index computed tomography scan are highly suggestive of acute-on-chronic CTEPH.
A prevalência da hipertensão pulmonar tromboembólica crónica (HPTEC) após embolia pulmonar aguda (EP) na população portuguesa permanece desconhecida. O objetivo do nosso trabalho foi avaliar a prevalência e os fatores de risco de HPTEC dois anos após uma EP sintomática de alto risco (A) e risco intermédio-alto (IA).
Estudo de coorte retrospetivo que inclui doentes admitidos com EP entre 2014-2019 num centro de referência nacional para hipertensão pulmonar.
Dos 969 doentes admitidos com EP (incidência anual de 46/100.000 habitantes), 194 foram estratificados como EP de risco A (5,4%) e IA (14,7%). Após exclusão dos doentes que faleceram ou sem seguimento nos primeiros três meses, 129 doentes foram incluídos na análise. A prevalência geral de HPTEC suspeita por avaliação clínica, ecocardiograma com Doppler e cintigrafia pulmonar de ventilação/perfusão foi de 6,2% (8 doentes). HPTEC foi confirmada por cateterismo cardíaco direito em quatro desses doentes (3,1%). A elevação da pressão sistólica da artéria pulmonar (PAPs) na admissão (OR 1,12; IC95% 1,04-1,22; p=0,005) e a presença de varizes nos membros inferiores (OR 7,47; IC95% 1,53-36,41; p=0,013) foram preditores de HPTEC. PAPs na admissão >60 mmHg identificou doentes com HPTEC no seguimento com valor de sensibilidade e especificidade de 83,3% e 76,3%, respetivamente. Todos os doentes diagnosticados com HPTEC tiveram pelo menos dois achados radiológicos sugestivos de HPTEC no evento índice.
Na nossa coorte, a prevalência de HPTEC nos sobreviventes de formas graves de EP aguda foi de 6,2%. Uma pressão arterial pulmonar sistólica acima de 60 mmHg e achados radiológicos de suporte na tomografia computadorizada do evento índice são altamente sugestivos da presença de HPTEC preexistente no momento do diagnóstico de EP aguda.
Enhancing preoperative assessment in chronic thromboembolic pulmonary hypertension: A comprehensive analysis of interobserver agreement and proximity-based CT pulmonary angiography scoring
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Surgical risk in chronic thromboembolic pulmonary hypertension (CTEPH) depends on the proximity of thromboembolism on CT pulmonary angiography (CTPA). We assessed interobserver agreement for the quantification of thromboembolic lesions in CTEPH using a novel CTPA scoring index.
Forty CTEPH patients (mean age, 58 ± 16 years; 19 men) with preoperative CTPA who underwent pulmonary endarterectomy (PEA) (08/2020-09/2021) were retrospectively included. Three radiologists scored each CTPA for chronic thromboembolism (occlusions, eccentric thickening, webs) using a 32-vessel model of the pulmonary vasculature, with interobserver agreement evaluated using Fleiss’ kappa. CT level of disease was determined by the most proximal chronic thromboembolism: level 1 (main pulmonary artery), 2 (lobar), 3 (segmental) and 4 (subsegmental), and compared to surgical level at PEA.
Interobserver agreement for CT level of disease was moderate overall (κ = 0.52). Agreement was substantial overall at the main/lobar level (κ, mean = 0.71) when excluding the left upper lobe (κ = 0.17). Though segmental and subsegmental agreement suffered (κ = 0.31), we found substantial agreement for occlusions (κ = 0.72) compared to eccentric thickening (κ = 0.45) and webs (κ = 0.14). Correlation between CT level and surgical level was strong overall (τb = 0.73) and in the right lung (τb = 0.68), but weak in the left lung (τb = 0.42) (p < 0.05). Radiologists often over- and underestimated the proximal extent of disease in right and left lung, respectively.
CT level of disease demonstrated good agreement between radiologists and was highly predictive of the surgical level in CTEPH. Occlusions were the most reliable sign of chronic thromboembolism and are important in assessing the segmental vasculature.
Chronic thromboembolic pulmonary hypertension: realising the potential of multimodal management
2023, The Lancet Respiratory Medicine
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism. Important advances have enabled better understanding, characterisation, and treatment of this condition. Guidelines recommending systematic follow-up after acute pulmonary embolism, and the insight that CTEPH can mimic acute pulmonary embolism on initial presentation, have led to the definition of CTEPH imaging characteristics, the introduction of artificial intelligence diagnosis pathways, and thus the prospect of easier and earlier CTEPH diagnosis. In this Series paper, we show how the understanding of CTEPH as a sequela of inflammatory thrombosis has driven successful multidisciplinary management that integrates surgical, interventional, and medical treatments. We provide imaging examples of classical major vessel targets, describe microvascular targets, define available tools, and depict an algorithm facilitating the initial treatment strategy in people with newly diagnosed CTEPH based on a multidisciplinary team discussion at a CTEPH centre. Further work is needed to optimise the use and combination of multimodal therapeutic options in CTEPH to improve long-term outcomes for patients.
Preexisting Chronic Thromboembolic Pulmonary Hypertension in Acute Pulmonary Embolism
2023, Chest
Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a complication of pulmonary embolism (PE). However, signs of CTEPH may exist in patients with a first symptomatic PE.
Which radiologic findings on CT pulmonary angiography (CTPA) at the time of acute PE could indicate the presence of preexisting CTEPH?
This study included unselected patients with acute PE who were prospectively followed up for 2 years with a structured visit schedule. Two expert radiologists independently assessed patients’ baseline CTPAs for preexisting CTEPH; in case of disagreement, a decision was reached by a 2:1 majority with a third expert radiologist. In addition, the radiologists checked for predefined individual parameters suggesting chronic PE and pulmonary hypertension.
Signs of chronic PE or CTEPH at baseline were identified in 46 of 303 included patients (15%). Intravascular webs, arterial narrowing or retraction, dilated bronchial arteries, and right ventricular hypertrophy were the main drivers of the assessment. Five (1.7%) patients were diagnosed with CTEPH during follow-up. All four patients diagnosed with CTEPH early (83-108 days following acute PE) were found in enriched subgroups based on the experts’ overall assessment or fulfilling a minimum number of the predefined radiologic criteria at baseline. The specificity of preexisting CTEPH diagnosis and the level of radiologists’ agreement improved as the number of required criteria increased.
Searching for predefined radiologic parameters suggesting preexisting CTEPH at the time of acute PE diagnosis may allow for targeted follow-up strategies and risk-adapted CTEPH screening, thus facilitating earlier CTEPH diagnosis.
Diagnostic efficacy of ECG-derived ventricular gradient for the detection of chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism
2022, Journal of Electrocardiology
Citation Excerpt :
Mainly, more focus on computed tomography pulmonary angiogram (CTPA) images at baseline may also help identifying patients with CTEPH early in the course of time. We and others showed that signs of chronicity, e.g. the presence of webs/bands, bronchial artery dilatation and right ventricle hypertrophy identified on CTPA images is a strong predictor of a future CTEPH diagnosis [35,36,38]. Indeed, these radiological signs are not effected by anticoagulation therapy and can be evaluated by CTEPH experts as well as by non-specifically trained board-certified radiologists [41–43].
Application of the chronic thromboembolic pulmonary hypertension (CTEPH) rule out criteria (manual electrocardiogram [ECG] reading and N-terminal pro-brain natriuretic peptide [NTproBNP] test) can rule out CTEPH in pulmonary embolism (PE) patients with persistent dyspnea (InShape II algorithm). Increased pulmonary pressure may also be identified using automated ECG-derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO).
A predefined analysis of the InShape II study was performed. The diagnostic performance of the VG-RVPO for the detection of CTEPH and the incremental diagnostic value of the VG-RVPO as new rule-out criteria in the InShape II algorithm were evaluated.
60 patients were included; 5 (8.3%) were ultimately diagnosed with CTEPH. The mean baseline VG-RVPO (at time of PE diagnosis) was −18.12 mV·ms for CTEPH patients and − 21.57 mV·ms for non-CTEPH patients (mean difference 3.46 mV·ms [95%CI −29.03 to 35.94]). The VG-RVPO (after 3–6 months follow-up) normalized in patients with and without CTEPH, without a clear between-group difference (mean Δ VG-RVPO of −8.68 and − 8.42 mV·ms respectively; mean difference of −0.25 mV·ms, [95%CI −12.94 to 12.44]). The overall predictive accuracy of baseline VG-RVPO, follow-up RVPO and Δ VG-RVPO for CTEPH was moderate to poor (ROC AUC 0.611, 0.514 and 0.539, respectively). Up to 76% of the required echocardiograms could have been avoided with VG-RVPO criteria replacing the InShape II rule-out criteria, however at cost of missing up to 80% of the CTEPH diagnoses.
We could not demonstrate (additional) diagnostic value of VG-RVPO as standalone test or as on top of the InShape II algorithm.

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Usefulness of standard computed tomography pulmonary angiography performed for acute pulmonary embolism for identification of chronic thromboembolic pulmonary hypertension: results of the InShape III study

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

Section snippets

Study population

Patients

Discussion

Disclosure statement

Blood

Chest

Chest

Clin Radiol

J Thromb Haemost

Chest

J Thromb Haemost

J Thromb Haemost

Thromb Res

Thromb Res

Eur Respir J

Update on chronic thromboembolic pulmonary hypertension

Circulation

Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature

Eur Respir J