Risk Factors For Chronic Thromboembolic Pulmonary Hypertension Research Articles

Post-Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline.

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation-perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

Abstract 10190: Recurrent Pulmonary Hypertension After Balloon Pulmonary Angioplasty in Patients With Inoperable Thromboembolic Pulmonary Hypertension

Backgrounds: Balloon pulmonary angioplasty (BPA) improves hemodynamics and prognosis in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Though it has been reported that recurrent pulmonary hypertension (PH) after pulmonary endarterectomy is rare, the recurrence rate of PH after BPA remains to be clarified. In this study, we examined the frequency of recurrent PH after BPA in the long-term period and the risk factors. Methods: We retrospectively reviewed consecutive 200 CTEPH patients (65±12yrs., Male 43(22%)) who completed BPA procedures from July 2009 to December 2020 and had hemodynamic evaluation after the procedures and extracted the patients with recurrent PH who had a mean pulmonary arterial pressure (mPAP) &lt;25 mm Hg after BPA and developed PH (mPAP ≥25 mm Hg) during follow-up and had a clinical deterioration requiring additional treatment. As risk factors for recurrent PH, we investigated the known risk factors for the development of CTEPH, and the types of oral anticoagulants (warfarin or direct oral anticoagulant). Results: The median follow-up period from final BPA session was 42 [24,62] months. BPA significantly improved mPAP (39±10 to 22±5mmHg, P&lt;0.01) and cardiac output (CO) (3.6±1.1 to 4.1±1.1 L/min, P&lt;0.01). Recurrent PH was observed in 13 of the 200 patients (6.5%) during the follow-up period and the estimated 5-year recurrence rate was 8.9%. The median period from final BPA to recurrence was 20 months [12,47 months], and 6 cases (46%) recurred PH within a year after BPA. In these patients, mPAP deteriorated from 21±2 to 29±5mmHg (P&lt;0.01) but not CO (4.07±0.69 to 3.81±0.50L/min, P=0.46). Of the 13 recurrent PH patients, 9 required additional BPA, and 6 required additional medication. However, the 5-year survival in the recurrent PH and non-recurrent PH groups were comparable (100% and 96.1%, P=0.50). Any risk factors for recurrent PH were not detected. The recurrence rate of PH in those with direct oral anticoagulant (83 cases (42%)) was similar to that in those with warfarin (3.6% and 8.6%, P=0.16). Conclusions: Recurrent PH after BPA is rare and not associated with the known risk factors for CTEPH. The prognosis in the recurrent PH group with additional treatments is similar to that in the non-recurrent group.

Dyspnea and perfusion defects (V/Q scan) are common after an acute pulmonary embolus whereas chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequele

Abstract Introduction Acute pulmonary embolism (PE), a common disease with substantial morbidity and mortality. Many previous studies have focused on the short-term consequences after an acute PE, but less attention has been directed to the long-term effects of a PE. The most feared complication is chronic thromboembolic pulmonary hypertension (CTEPH), with reported incidence rates ranging from 0.6 to 4.8%. Even though CTEPH is a rare complication after PE, dyspnea and functional impairment are common complaints, and a syndrome named PPES (post-PE-syndrome) has been suggested. The aim of this study was to follow a large national-wide cohort of post-PE-patients and to gather information regarding long-term symptoms and to determine the prevalence of CTEPH. Patients and methods We identified all patients diagnosed with acute PE in 2005 (ICD-10-SE: I26.0 and I26.9) that were registered in the Swedish National Patient Register (NPR), which has nearly 100% coverage. In 2007, all surviving individuals were invited to participate by letter. They were asked to complete a questionnaire regarding symptoms and risk factors for long-term sequele including CTEPH. Individuals who reported dyspnea or had known risk factors for CTEPH were invited to a follow-up with blood tests (NT-pro-BNP) and pulmonary scintigraphy. If any perfusion defects were detected, an echocardiography was performed. If signs of pulmonary hypertension, a referral was done to the regional PAH-center. Results In 2005, 5793 unique patients were admitted with a PE diagnosis in Sweden. Of those, 3510 were still alive in 2007, and 3226 individuals were contacted and asked to complete the questionnaire. Altogether 2105 (65%) individuals returned the questionnaire, and 53% reported dyspnea and 15% were asymptomatic but had risk factors for CTEPH. Altogether 944 individuals were referred for further follow-up including a recommendation to perform a V/Q-scan. Altogether 530 V/Q-scans were performed and 44% showed perfusion defects, whereof 85% had an echocardiography. Twenty-seven % of them registered a systolic right ventricular pressure of at least 30 mmHg. Referrals resulted in 6 cases with proved CTEPH. In parallel, 10 patients with CTEPH diagnosed before 2005 were detected, and 8 patients were diagnosed after 2005 and outside the study.Altogether 24 patients with CTEPH were thus identified and the cumulative incidence of CTEPH ranged between 0.7 and 1.2%. Conclusion Dyspnea is common after an acute PE and over 40% of them have perfusion defects on a V/Q scan, suggesting the presence of a post PE-syndrome (PPES). The incidence of CTEPH is however low. More research is needed to better define PPES. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Actelion PharamceuticalsSwedish Heart and Lung Foundation

Abstract No. 278 Evaluation of chronic sequelae of pulmonary embolism in cancer patients: a population health analysis

The long-term consequences of non-fatal PE in cancer patients such as chronic thromboembolic pulmonary hypertension (CTEPH) are not well understood. It is unclear whether cancer patients would benefit from interventions such as pulmonary thrombectomy to prevent this complication. The purpose of this study was to evaluate the incidence and risk factors for CTEPH in cancer patients with PE.

Characteristics of chronic thromboembolic pulmonary hypertension in Ireland.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and under-recognised complication of acute pulmonary embolism. Information regarding the characteristics of CTEPH in Ireland is limited, and the aim of this retrospective cohort study was to address this knowledge gap. Seventy-two cases of CTEPH were diagnosed in the National Pulmonary Hypertension Unit (NPHU) in Ireland between 2010 and 2020. This accounted for 6% of all referrals to the unit and translates to an estimated annual incidence of 1.39 per million population (95% confidence interval, 0.33–2.46). The prevalence of diagnosed CTEPH in Ireland in 2020 was estimated at 12.05 per million population (95% CI 9.00–15.10). The average duration of symptoms prior to CTEPH diagnosis was 23 (±22) months. Patients with CTEPH were more likely to be male (n = 40, 56%), older (60 ± 17 years) and have identifiable risk factors for CTEPH (n = 61, 85%) at diagnosis. Regarding treatment, pulmonary hypertension (PH) vasodilator therapy was prescribed in 75% (n = 54) within 12 months of diagnosis, inferior vena cava filters were placed in 24% (n = 17) and 97% (n = 70) of cases were anticoagulated. Pulmonary endarterectomy was performed in 35% (n = 25), balloon pulmonary angioplasty in 6% (n = 4). One-, three- and five-year survival was 93%, 80% and 65% from the time of diagnosis, and this was significantly better in patients who underwent pulmonary endarterectomy (p = 0.01). This is the first study describing the characteristics of CTEPH in Ireland and highlights suboptimal disease recognition and referral for the assessment for pulmonary endarterectomy.

Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism.

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.

Investigation of prognostic effect of red cell distribution width on chronic thromboembolic pulmonary hypertension in patients with acute pulmonary embolism

Objective To investigate the clinical characteristics of acute pulmonary embolism in the elderly and its differences between the elderly and non-elderly patients, and explore the predictive effect of red blood cell distribution width(RDW)on chronic thromboembolic pulmonary hypertension(CTEPH)in patients with acute pulmonary embolism. Methods A total of 129 consecutive patients with acute pulmonary embolism admitted into Affiliated Hospital of Binzhou Medical College were selected from Jan.2009 to Dec.2013.Clinical data including the basic data, blood routine test, blood gas analysis, Doppler echocardiography during admission were retrospectively analyzed.All the patients were followed-up.Ancillary findings and changes of the disease were recorded in detail during the follow-up period.SPSS 19.0 was used to analyze the results. Results The incidences of CEPPH and venous thromboembolism(VTE)in APE patients were higher in the elderly than in non-elderly.The mean RDW and pulmonary arterial systolic pressure on admission in APE patients were higher in the elderly than in non-elderly [(14.22±2.11)% vs.(13.48±1.69)%, P=0.033, for mean RDW] and [(54.82±21.77)mmHg vs.(42.20±19.36)mmHg, P=0.010 for pulmonary arterial systolic pressure]. The mean RDW was higher in CTEPH patients than in patients without CTEPH [(16.79±3.08)% vs.(13.68±1.68)%, P=0.016]. Multivariate Logistic analyses showed that the increased RDW level was an independent risk factors for CTEPH in APE patients(OR=1.535, 95% CI: 1.094-2.155, P=0.013). The area under receiver operating characteristics curve(AUC)of RDW level for predicting CTEPH in APE patients was 0.856(95% CI: 0.706-0.987, P<0.001), the corresponding cut-off point was 14.85%, and the sensitivity and specificity were 88.9% and 87.5% respectively. Conclusions The increased RDW level could predict the risk of CTEPH to a certain extent in APE patients. Key words: Pulmonary embolism; Hypertension, pulmonary; Erythrocytes

Incidence and risk factors of chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism.

Early identification and treatment of chronic thromboembolic pulmonary hypertension (CTEPH) are critical to prevent disease progression. We determined the incidence and risk factors for CTEPH in patients with a first episode of acute pulmonary embolism (PE). In this study, consecutive patients with first-episode acute PE were followed for ≤5 years. Pulmonary hypertension (PH) was screened for by echocardiography. Suspected cases were evaluated by right heart catheterization (RHC) and pulmonary angiography (PA). If invasive procedures were not permitted, PH was diagnosed by systolic pulmonary artery pressure (SPAP) >50 mmHg. Diagnosis of CTEPH was confirmed by PA, ventilation/perfusion (V/Q) lung scan, or computed tomography (CT) PA (CTPA). Overall, 614 patients with acute PE were included (median follow-up, 3.3 years). Ten patients were diagnosed with CTEPH: cumulative incidence 0.8% [95% confidence interval (CI), 0.0-1.6%] at 1 year, 1.3% (95% CI, 0.3-2.3%) at 2 years, and 1.7% (95% CI, 0.7-2.7%) at 3 years. No cases of CTEPH developed after 3 years. History of lower-limb varicose veins [hazard ratio (HR), 4.3; 95% CI, 1.2-15.4; P=0.024], SPAP >50 mmHg at initial PE episode (HR, 23.5; 95% CI, 2.7-207.6; P=0.005), intermediate-risk PE (HR, 1.2; 95% CI, 1.0-1.4; P=0.030), and CT obstruction index over 30% at 3 months after acute PE (HR, 42.5; 95% CI, 4.4-409.8; P=0.001) were associated with increased risk of CTEPH. CTEPH was not rare after acute PE in this Chinese population, especially within 3 years of diagnosis. Lower-limb varicose veins, intermediate-risk PE with elevated SPAP in the acute phase, and residual emboli during follow-up might increase the risk of CTEPH.

Infarctus pulmonaires excavés révélant une hypertension pulmonaire post-embolique

Several etiologies are involved in the pathogenesis of cavitating pulmonary disease including neoplastic, infectious or inflammatory processes. Another is pulmonary infarction associated with venous thromboembolism. The lung cavities tend to be located peripherally and are the result of pulmonary embolism. We report the case of a woman with chronic thromboembolic pulmonary hypertension (CTEPH), associated with familial thrombophilia, revealed by cavitating pulmonary infarcts. CTEPH is sometimes diagnosed during an episode of recurrent pulmonary embolism following previously unnoticed lesions. Thrombophilias such as isolated elevated factor VIII are risk factors for CTEPH.

HLA-DPB1 and NFKBIL1 may confer the susceptibility to chronic thromboembolic pulmonary hypertension in the absence of deep vein thrombosis

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by pulmonary hypertension caused by thromboembolism of the pulmonary artery. Etiology of CTEPH may be heterogeneous and is largely unknown, but genetic factors are considered to be involved in the etiology. It has been reported that deep vein thrombosis (DVT) and/or coagulation factor variants are predisposing factors to CTEPH. However, more than half of the CTEPH patients, especially the Japanese, do not have prior DVT or coagulation abnormality, suggesting that there should be other risk factors for CTEPH. Moreover, there are several reports on the association between CTEPH and human leukocyte antigen (HLA). To further clarify the HLA-linked gene(s) controlling the susceptibility to CTEPH, 160 patients (99 without DVT and 61 with DVT) and 380 healthy controls were analyzed for polymorphisms in 15 microsatellite markers and 5 genes in the HLA region. We found a strong association of HLA markers with the DVT-negative CTEPH, DPB1(*)0202 (odds ratio (OR)=5.07, 95% confidence interval (CI)=2.52-10.19, P=0.00000075, corrected P-value (Pc)=0.00014), IKBL-p(*)03 (OR=2.33, 95% CI=1.49-3.66, P=0.00017, Pc=0.033) and B(*)5201 (OR=2.47, 95% CI=1.56-3.90, P=0.000086, Pc=0.016), whereas no significant association was observed for the DVT-positive CTEPH. The comparison of clinical characteristics of patients stratified by the presence of susceptibility genes implied that the DPB1 gene controlled the severity of the vascular lesion, whereas the IKBL gene (NFKBIL1) was associated with a relatively mild phenotype.