P2612Determinants of diagnostic delay in chronic thromboembolic pulmonary hypertension: results from the international prospective cteph registry

Abstract Background The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE) is unacceptably long exceeding 1 year, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies to diagnose CTEPH earlier are lacking. Importantly, performing echocardiography in all PE patients for this purpose has a low diagnostic yield, is associated with overdiagnosis and is not cost-effective. Moreover, expertise in performing high-quality PH-dedicated echocardiograms may not be available outside expert centers. Aim To validate a simple screening strategy aimed at identifying CTEPH early in the course after acute PE, avoiding echocardiography if possible (Figure 1). Methods In this prospective, international, multicenter management study, consecutive PE survivors were managed according to the predefined algorithm starting three months after acute PE. All were followed for a total period of two years. The study protocol was approved by all local IRBs and all patients provided informed consent. Results 424 patients were included across three European countries (Table 1). Following the algorithm, CTEPH was considered excluded in 343 (81%) patients based on clinical pre-test probability assessment by the “CTEPH prediction score”, evaluation of symptoms and application of the “CTEPH rule-out criteria” (Figure 1); only 19% was subjected to echocardiography. Only 1 of 343 patients managed without echocardiography was diagnosed with CTEPH, 10 months after initial PE, for a failure rate of 0.29% (95% CI 0–1.6%). Overall, 13 patients were diagnosed with CTEPH (incidence 3.1%), of whom 10 within 4 months after PE diagnosis. Conclusions The algorithm accurately ruled out CTEPH and avoided echocardiography in 81% of patients. The vast majority of CTEPH cases were identified early in the course of acute PE which is a considerable improvement compared to current clinical practice with an economic use of healthcare resources. Figure 1. Study flowchart Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): This study was supported by unrestricted grants from Bayer/Merck Sharp & Dohme (MSD) and Actelion Pharmaceuticals Ltd. F.A. Klok and G.J.A.M. Boon were supported by the Dutch Heart Foundation (2017T064).

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Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism

European Respiratory Journal ◽

10.1183/13993003.00189-2020 ◽

2020 ◽

Vol 55 (6) ◽

pp. 2000189 ◽

Cited By ~ 7

Author(s):

Fredrikus A. Klok ◽

Francis Couturaud ◽

Marion Delcroix ◽

Marc Humbert

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Hypertension ◽

Clinical Practice ◽

Acute Pulmonary Embolism ◽

Functional Limitations ◽

Diagnostic Delay ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Pulmonary Endarterectomy ◽

Thromboembolic Pulmonary Hypertension ◽

Clear Guideline

Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). Untreated CTEPH is fatal, but, if diagnosed in time, successful surgical (pulmonary endarterectomy), medical (pulmonary hypertension drugs) and/or interventional (balloon pulmonary angioplasty) therapies have been shown to improve clinical outcomes, especially in case of successful pulmonary endarterectomy. Early diagnosis has however been demonstrated to be challenging. Poor awareness of the disease by patients and physicians, high prevalence of the post-PE syndrome (i.e. persistent dyspnoea, functional limitations and/or decreased quality of life following an acute PE diagnosis), lack of clear guideline recommendations as well as inefficient application of diagnostic tests in clinical practice lead to a reported staggering diagnostic delay >1 year. Hence, there is a great need to improve current clinical practice and diagnose CTEPH earlier. In this review, we will focus on the clinical presentation of and risk factors for CTEPH, and provide best practices for PE follow-up programmes from expert centres, based on a clinical case.

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Determinants of diagnostic delay in chronic thromboembolic pulmonary hypertension: results from the European CTEPH Registry

European Respiratory Journal ◽

10.1183/13993003.01687-2018 ◽

2018 ◽

Vol 52 (6) ◽

pp. 1801687 ◽

Cited By ~ 12

Author(s):

Frederikus A. Klok ◽

Stefano Barco ◽

Stavros V. Konstantinides ◽

Philippe Dartevelle ◽

Elie Fadel ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Diagnostic Delay ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Thromboembolic Pulmonary Hypertension

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Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study

Thorax ◽

10.1136/thoraxjnl-2020-216324 ◽

2021 ◽

pp. thoraxjnl-2020-216324

Author(s):

Gudula J A M Boon ◽

Yvonne M Ende-Verhaar ◽

Roisin Bavalia ◽

Lahassan H El Bouazzaoui ◽

Marion Delcroix ◽

...

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Hypertension ◽

Diagnostic Delay ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Screening Strategy ◽

Echocardiographic Evaluation ◽

Life Years ◽

Thromboembolic Pulmonary Hypertension ◽

Acute Pe ◽

Rule Out

Background The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms. Methods In this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the ‘CTEPH prediction score’ indicated high pretest probability or matching symptoms were present, the ‘CTEPH rule-out criteria’ were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography. Results 424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation. Conclusions The InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.

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A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension

ERJ Open Research ◽

10.1183/23120541.00719-2020 ◽

2021 ◽

pp. 00719-2020

Author(s):

Gudula J.A.M. Boon ◽

Wilbert B. van den Hout ◽

Stefano Barco ◽

Harm Jan Bogaard ◽

Marion Delcroix ◽

...

Keyword(s):

Health Economic ◽

Pulmonary Hypertension ◽

Healthcare Costs ◽

Diagnostic Delay ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Life Years ◽

Hypothetical Scenario ◽

Dutch Health ◽

Thromboembolic Pulmonary Hypertension ◽

The Impact

BackgroundDiagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds >1 year, contributing to higher mortality. Health-economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life years (QALYs) and healthcare costs.Material and methodsA Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC - VUmc, which is a Dutch CTEPH referral center. Medication costs were based on a mix of standard medication regimens.ResultsFor 63-year-old CTEPH patients with a 14 months diagnostic delay of CTEPH (median age and delay of patients in the European CTEPH Registry), lifelong healthcare costs were estimated at €117 100 for a mix of treatment options. In a hypothetical scenario of maximal reduction of current delay, improved survival was estimated at a gain of 3.01 life years and 2.04 QALYs. The associated cost increase was €44 654, of which 87% was due to prolonged medication use. This accounts for an incremental cost-utility ratio of €21 900/QALY.ConclusionOur constructed model based on the Dutch healthcare setting demonstrates a substantial health gain when CTEPH is diagnosed earlier. According to Dutch health-economic standards, additional costs remain below the deemed acceptable limit of €50 000/QALY for the particular disease burden. This model can be used for evaluating cost-effectiveness of diagnostic strategies aimed at reducing the diagnostic delay.

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Why, Whom, and How to Screen for Chronic Thromboembolic Pulmonary Hypertension after Acute Pulmonary Embolism

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0040-1718925 ◽

2020 ◽

Author(s):

Gudula J. A. M. Boon ◽

Menno V. Huisman ◽

Frederikus A. Klok

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Hypertension ◽

Acute Pulmonary Embolism ◽

Negative Impact ◽

Screening Program ◽

Diagnostic Delay ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Population Based ◽

Novel Approach ◽

Thromboembolic Pulmonary Hypertension

AbstractChronic thromboembolic pulmonary hypertension (CTEPH) is considered a long-term complication of acute pulmonary embolism (PE). Diagnosing CTEPH is challenging, as demonstrated by a considerable diagnostic delay exceeding 1 year, which has a negative impact on the patient's prognosis. Dedicated screening CTEPH strategies in PE survivors could potentially help diagnosing CTEPH earlier, although the optimal strategy is unknown. Recently published updated principles for screening in medicine outline the conditions that must be considered before implementation of a population-based screening program. Following these extensive principles, we discuss the pros and cons of CTEPH screening, touching on the epidemiology of CTEPH, the prognosis of CTEPH in the perspective of emerging treatment possibilities, and potentially useful tests and test combinations for screening. This review provides a modern perspective on CTEPH screening including a novel approach using a simple noninvasive algorithm of sequential diagnostic tests applied to all PE survivors.

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