Abstract
Chronic thromboembolic disease diagnosed following acute pulmonary embolism warrants refinement of its definition and further evaluation of optimal anticoagulation strategies http://bit.ly/38SQXc0
To the Editor:
The recently updated European Society of Cardiology/European Respiratory Society guidelines for acute pulmonary embolism (PE) underline the importance of appropriate long-term management of PE sequelae in the era of extended anticoagulation [1]. Chronic thromboembolic disease (CTED) is one of several conditions contributing to breathlessness in this setting, i.e. persistent pulmonary vascular obstruction on imaging, with no evidence of pulmonary hypertension at rest. CTED is increasingly encountered in pulmonary vascular disease clinics following acute PE, and its diagnosis relies heavily on careful exclusion of other conditions that may contribute to symptoms. Given the need for careful follow-up after PE, in this paper we highlight two important points relating to the diagnosis and management of CTED: firstly, the location and extent of chronic pulmonary artery thrombus on imaging and secondly, the lack of evidence to support long-term anticoagulation in CTED, as opposed to chronic thromboembolic pulmonary hypertension (CTEPH).
The haemodynamic definition of CTED includes patients with evidence of pulmonary vascular obstruction and a mean pulmonary artery pressure <25 mmHg at rest assessed by right heart catheterisation [2]. In line with CTEPH, the diagnosis of CTED usually requires at least 3 months anticoagulation prior to the diagnostic work-up. The original description of CTED as a novel diagnosis, distinct from CTEPH, included highly selected symptomatic patients referred for pulmonary endarterectomy (PEA) on account of a large thrombotic burden on computed tomography (CT) pulmonary angiography (CTPA), mild right ventricle (RV) enlargement on echocardiography, but no pulmonary hypertension at rest [3]. The same research group later reported clinical improvement in terms of World Health Organization functional class and quality of life scores following surgery in a more extended CTED cohort [4]. Recently, the diagnostic definition of CTED has transformed to encompass breathless patients following acute PE who, despite anticoagulation, demonstrate persistent areas of perfusion/ventilation mismatch on nuclear scintigraphy, irrespective of the presence or location of thrombus on CT.
In broadening the clinical definition to include patients with distal vascular obstruction, more patients are being diagnosed with CTED. Pulmonary vascular resistance (PVR) is usually minimally affected by anatomical thrombus distribution. However, impedance to pulmonary forward flow is not well-captured by PVR and may be markedly different between patients with proximal versus distant lesions, with a greater effect on RV afterload arising from proximal pulmonary vascular obstruction [5, 6]. Discrimination between proximal thrombus on CT and more distal obstruction on scintigraphy may, therefore, be important in defining the haemodynamic effect of CTED, and its impact on the RV and symptoms.
Secondly, anticoagulation in CTEPH is prescribed under a class 1 recommendation, and recourse to extended anticoagulation in CTED is extrapolated from this guideline [2]. However, when a diagnosis of CTED is made after an index PE associated with a major transient risk factor, such as immobilisation related to surgery, clinical uncertainty arises and the decision to pursue extended anticoagulation may not automatically apply. “Post-PE syndrome” has recently been introduced to describe permanent changes in pulmonary artery flow, gas exchange and/or cardiac function in the breathless patient following PE. While this entity links symptoms to abnormal gas exchange and RV dysfunction, definitive anticoagulation recommendations are lacking [7]. We have learnt from the ELOPE study that post-PE breathlessness is unrelated to both clot burden and choice of anticoagulation [8]; however, low levels of pulmonary vascular obstruction in this study leave unanswered questions around optimal anticoagulation strategies in patients with larger thrombotic burden after PE.
In our view, the current diagnostic landscape appears too broad to allow emergence of meaningful clinical guidance on CTED management. To streamline this approach, we suggest a diagnostic label of CTED be reserved for symptomatic patients with chronic proximal thrombus on CTPA in whom, in the alternative context of pulmonary hypertension, clinicians would consider surgical referral for PEA. In our experience, such patients more frequently exhibit mild RV dilatation on echocardiography than those without proximal thrombus on CTPA and are more likely to benefit from prolonged anticoagulation irrespective of PE risk factors. In contrast, symptomatic patients with isolated perfusion defects on nuclear scintigraphy at 3–6 months following PE with no proximal thrombotic burden on CTPA require prospective evaluation within anticoagulation studies, grouped by the presence of transient risk factors at the time of PE and/or risk factors for CTEPH. We therefore propose an algorithm formulated from our clinical experience (figure 1), in which a diagnosis of CTED becomes the preserve of pulmonary hypertension expert centres where exercise haemodynamic evaluation, PEA referral or balloon pulmonary angioplasty can be offered [9, 10]. This algorithm, currently untested in management studies, simplifies the differentiation between CTED and post-PE breathlessness at 3–6 months follow-up by sole reliance on imaging without the need for cardiopulmonary exercise testing which carries greater variability in interpretation. With few individuals eligible for PEA, anticoagulation remains the only medical therapy that may be offered to most CTED patients. Criteria for the identification of patients who are likely to benefit from extended anticoagulation, versus those who may safely discontinue treatment with no detriment to their quality of life or risk of PE recurrence, will only emerge with a more robust definition of CTED in this diverse patient population.
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Footnotes
Conflict of interest: C. McCabe has nothing to disclose.
Conflict of interest: K. Dimopoulos has nothing to disclose.
Conflict of interest: A. Pitcher has nothing to disclose.
Conflict of interest: E. Orchard has nothing to disclose.
Conflict of interest: L.C. Price has nothing to disclose.
Conflict of interest: A. Kempny has nothing to disclose.
Conflict of interest: S.J. Wort has nothing to disclose.
- Received October 1, 2019.
- Accepted January 24, 2020.
- Copyright ©ERS 2020