The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is relevant for management decisions but is currently unknown.We performed a meta-analysis of ...studies including consecutive PE patients followed for CTEPH. Study cohorts were predefined as "all comers", "survivors" or "survivors without major comorbidities". CTEPH incidences were calculated using random effects models.We selected 16 studies totalling 4047 PE patients who were mostly followed up for >2-years. In 1186 all comers (two studies), the pooled CTEPH incidence was 0.56% (95% CI 0.1-1.0). In 999 survivors (four studies) CTEPH incidence was 3.2% (95% CI 2.0-4.4). In 1775 survivors without major comorbidities (nine studies), CTEPH incidence was 2.8% (95% CI 1.5-4.1). Both recurrent venous thromboembolism and unprovoked PE were significantly associated with a higher risk of CTEPH, with odds ratios of 3.2 (95% CI 1.7-5.9) and 4.1 (95% CI 2.1-8.2) respectively. The pooled CTEPH incidence in 12 studies that did not use right heart catheterisation as the diagnostic standard was 6.3% (95% CI 4.1-8.4).The 0.56% incidence in the all-comer group probably provides the best reflection of the incidence of CTEPH after PE on the population level. The ∼3% incidences in the survivor categories may be more relevant for daily clinical practice. Studies that assessed CTEPH diagnosis by tests other than right heart catheterisation provide overestimated CTEPH incidences.
Right ventricular (RV) dysfunction caused by acute pulmonary embolism (PE) is associated with poor short- and long-term prognosis. RV dilatation as a proxy for RV dysfunction can be assessed by ...calculating the right-to-left ventricle diameter (RV/LV) ratio on standard computed tomography pulmonary angiography (CTPA) images. It is unknown whether dedicated training is required to accurately and reproducibly measure RV/LV ratio therefore we aimed to assess these parameters in residents in internal medicine without experience in CTPA reading.
CTPA images of 100 patients with PE were assessed by three residents after single instruction, and one experienced thoracic radiologist. Maximum diameters were evaluated in the axial view by measuring the distance between the ventricular endocardium and the interventricular septum, perpendicular to the long axis of the heart. RV dilatation was defined as a ratio of ≥1.0. Interobserver accuracy and reproducibility was determined using Kappa statistics, Bland-Altman analysis and Spearman's rank correlation.
The kappa statistic for the presence of RV dilatation of the residents compared to the experienced radiologist ranged from 0.83-0.94. The average interobserver difference in calculated RV/LV ratio's (±SD) between the three residents was: -0.01 (SD0.11), 0.07 (SD0.14) and 0.06 (SD0.18) with an overall mean RV/LV diameter ratio of 1.04. In line with this, Spearman's rank correlation coefficients were 0.92, 0.88 and 0.85 respectively indicating very good correlation (p<0.01 for all).
After simple instruction, RV/LV diameter ratio assessment on CTPA images by clinical residents is accurate and reproducible, which is of help in identifying PE patients at risk.
The pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary ...embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis.
Case-control study in which the time spent in, under and above therapeutic range was calculated in 44 PE patients who were subsequently diagnosed with CTEPH (cases). Controls comprised 150 consecutive PE patients in whom echocardiograms two years later did not show pulmonary hypertension. All patients were treated with VKA for at least 6 months after the PE diagnosis. Time in (TTR), under and above range were calculated. Mean differences between cases and controls were estimated by linear regression.
Mean TTR during the initial 6-month treatment period was 72% in cases versus 78% in controls (mean difference -6%, 95%CI -12 to -0.1), mainly explained by more time above the therapeutic range in the cases. Mean difference of time under range was 0% (95%CI -6 to 7) and 2% (95CI% -3 to 7) during the first 3 and 6 months, respectively. In a multivariable model, adjusted odds ratios (ORs) for CTEPH were around unity considering different thresholds for 'poor anticoagulation', i.e. TTR <50%, <60% and <70%.
Subtherapeutic initial anticoagulation was not more prevalent among PE patients diagnosed with CTEPH than in those who did not develop CTEPH.
Controversial reports exist in the literature regarding the prognostic role and therapeutic implications of syncope in patients with acute pulmonary embolism (PE). We conducted a systematic review ...and meta-analysis to investigate the association between syncope and short-term adverse outcomes, taking into account the presence or absence of haemodynamic compromise at acute PE presentation.
The literature search identified 1664 studies, 29 of which were included for a total of 21 956 patients with PE (n = 3706 with syncope). Syncope was associated with higher prevalence of haemodynamic instability odds ratio (OR) 3.50; 95% confidence interval (CI) 2.67-4.58, as well as with echocardiographic signs of right ventricular (RV) dysfunction (OR 2.10; CI 1.60-2.77) at presentation. Patients with syncope had a higher risks of all-cause early (either in-hospital or within 30 days) death (OR 1.73; CI 1.22-2.47) and PE-related 30-day adverse outcomes (OR 2.00; CI 1.11-3.60). The absolute risk difference (95% CI) for all-cause death was +6% (+1% to +10%) in studies including unselected patients, but it was -1% (-2% to +1%) in studies restricted to normotensive patients. We observed no prognostic impact of syncope in studies with a lower score at formal quality assessment and in those conducted retrospectively.
Syncope as a manifestation of acute PE was associated with a higher prevalence of haemodynamic instability and RV dysfunction at presentation, and an elevated risk for early PE-related adverse outcomes. The association with an increased risk of early death appeared more prominent in studies including unselected patients, when compared with those focusing on normotensive patients only.
Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long term complication of acute pulmonary embolism (PE). Untreated, CTEPH is associated with a very poor prognosis ...and high risk of mortality, although curation can be achieved by surgical removal of the obstructive endothelialised thromboemboli from the pulmonary arteries. Early CTEPH diagnosis may improve surgical possibilities and patients outcome. Currently, early diagnosis of CTEPH is a major challenge as demonstrated by an unacceptable median diagnostic delay of over a year and as a result, surgery is impossible in 40% of patients. Most important reasons for this delay are the non-specific clinical presentation of CTEPH and lack of guideline recommendations with regard to the optimal follow-up of patients with acute PE. Despite compelling reasons to diagnose CTEPH earlier, acute PE is not classified among the conditions that warrant screening for pulmonary hypertension. Meaningful screening programs improve the patients
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prognosis, and screening tools should be simple, widely available, non-invasive and acceptable to patients. In this review, we discuss current knowledge of available screening instruments for CTEPH, provide recommendations for clinical practice and expand on future developments of this particular subject.
BackgroundThe 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.MethodsIn 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.Results424 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.ConclusionsThe 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.
Objectives
Closer reading of computed tomography pulmonary angiography (CTPA) scans of patients presenting with acute pulmonary embolism (PE) may identify those at high risk of developing chronic ...thromboembolic pulmonary hypertension (CTEPH). We aimed to validate the predictive value of six radiological predictors that were previously proposed.
Methods
Three hundred forty-one patients with acute PE were prospectively followed for development of CTEPH in six European hospitals. Index CTPAs were analysed post hoc by expert chest radiologists blinded to the final diagnosis. The accuracy of the predictors using a predefined threshold for ‘high risk’ (≥ 3 predictors) and the expert overall judgment on the presence of CTEPH were assessed.
Results
CTEPH was confirmed in nine patients (2.6%) during 2-year follow-up. Any sign of chronic thrombi was already present in 74/341 patients (22%) on the index CTPA, which was associated with CTEPH (OR 7.8, 95%CI 1.9–32); 37 patients (11%) had ≥ 3 of 6 radiological predictors, of whom 4 (11%) were diagnosed with CTEPH (sensitivity 44%, 95%CI 14–79; specificity 90%, 95%CI 86–93). Expert judgment raised suspicion of CTEPH in 27 patients, which was confirmed in 8 (30%; sensitivity 89%, 95%CI 52–100; specificity 94%, 95%CI 91–97).
Conclusions
The presence of ≥ 3 of 6 predefined radiological predictors was highly specific for a future CTEPH diagnosis, comparable to overall expert judgment, while the latter was associated with higher sensitivity. Dedicated CTPA reading for signs of CTEPH may therefore help in early detection of CTEPH after PE, although in our cohort this strategy would not have detected all cases.
Key Points
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Three expert chest radiologists re-assessed CTPA scans performed at the moment of acute pulmonary embolism diagnosis and observed a high prevalence of chronic thrombi and signs of pulmonary hypertension.
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On these index scans, the presence of
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3 of 6 predefined radiological predictors was highly specific for a future diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), comparable to overall expert judgment.
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Dedicated CTPA reading for signs of CTEPH may help in early detection of CTEPH after acute pulmonary embolism.
The reported incidences of post-thrombotic syndrome (PTS) after deep vein thrombosis (DVT) vary. Further, PTS symptom development over time and its long-term incidence are unknown.
Patients included ...in the MEGA study were interviewed at 1 year and completed a questionnaire at 8 years of follow-up regarding symptoms and signs of PTS based on the Villalta score after a first DVT diagnosis. The cumulative incidence of PTS at 0–1 and 1–8 year, changes in PTS classification and the effect of possible clinical and laboratory risk factors were determined.
After 1 year, 361 out of 1657 patients diagnosed with DVT were classified as having PTS, for a 0–1 year cumulative incidence of 21.8% (95%CI 19.9–23.8), out of whom 92 (5.6%) had severe PTS. After 8 years 633 patients without previous PTS completed the second questionnaire, of whom 44 were classified as having PTS, for a 1–8 year cumulative incidence of 7% (95%CI 5.2–9.2); of these 13 (2.1%) were classified as severe PTS. During follow-up PTS complaints improved in 69% and worsened in 7% of patients. At 1 year, risk factors were female sex (RR 1.5; 95%CI 1.2–1.9) and obesity (RR 1.5; 95%CI 1.2–7.9), with the same effect sizes at 8 years. Provoked/unprovoked DVT, thrombus location, pregnancy, hormone use and several laboratory parameters did not affect risk of PTS, either at 1 or 8 years.
The incidence of PTS remained substantial up to 8 years after a first DVT. Symptoms improved in a large proportion of the cases. The short and long term risks were highest in women and obese patients.
•The incidence of and risk factors for PTS of the leg are debated.•1 and 8 years after DVT we scored patients on PTS based on the Villalta score.•0–1 and 1–8 year PTS incidences were 21.8% and 7.0% respectively.•PTS symptoms improved in 69% of patients.•Relevant risk factors for PTS were female sex and obesity (BMI > 30 kg m−2).
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