Pulmonary thromboendarterectomy (PTE) is the current gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH) and is a viable treatment option for chronic thromboembolic pulmonary disease (CTEPD). The progressive nature of both diseases severely impacts health-related quality of life (HRQoL) across a variety of domains. This systematic review was performed to evaluate the impact of PTE on short- and long-term HRQoL. A literature search was conducted on PubMed for studies matching the eligibility criteria between January 2000 and September 2022. OVID (MEDLINE), Google Scholar, EBSCOhost (EMBASE), and bibliographies of included studies were reviewed. Inclusion of studies was based on predetermined eligibility criteria. Quality appraisal and data tabulation were performed using predetermined forms. Results were synthesized by narrative review. The structure of this systematic review follows the PRISMA guidelines. This systematic review was prospectively registered in the PROSPERO register (CRD42022342144). Thirteen studies (2184 patients) were included. Within 3 months post-PTE, HRQoL improved in both CTEPD and CTEPH as measured by disease-specific and generic questionnaires. HRQoL improvements were sustained up to 5 years postoperatively in patients with CTEPH post-PTE. PTE remains the gold standard for treating CTEPH and improving HRQoL. Residual pulmonary hypertension and comorbidities such as COPD and coronary artery disease decrement HRQoL over time. The impact of mPAP and PVR on HRQoL outcomes postoperatively remain ambiguous. Pulmonary thromboendarterectomy remains the gold standard for treating CTEPH and has shown to improve HRQoL outcomes at 3-month sustaining improvements up to 5-year postoperatively. Residual pulmonary hypertension and comorbidities hinder HRQoL outcomes post-PTE.

Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.

Chronic thromboembolic pulmonary disease results from the incomplete resolution of thrombi, leading to fibrotic obstructions. These vascular obstructions and additional microvasculopathy may lead to chronic thromboembolic pulmonary hypertension (CTEPH) with increased pulmonary arterial pressure and pulmonary vascular resistance, which, if left untreated, can lead to right heart failure and death. The pathobiology of CTEPH has been challenging to unravel due to its rarity, possible interference of results with anticoagulation, difficulty in selecting the most relevant study time point in relation to presentation with acute pulmonary embolism (PE), and lack of animal models. In this article, we review the most relevant multifaceted cross-talking pathogenic mechanisms and advances in understanding the pathobiology in CTEPH, as well as its challenges and future direction. There appears to be a genetic background affecting the relevant pathological pathways. This includes genetic associations with dysfibrinogenemia resulting in fibrinolysis resistance, defective angiogenesis affecting thrombus resolution, and inflammatory mediators driving chronic inflammation in CTEPH. However, these are not necessarily specific to CTEPH and some of the pathways are also described in acute PE or deep vein thrombosis. In addition, there is a complex interplay between angiogenic and inflammatory mediators driving thrombus non-resolution, endothelial dysfunction, and vascular remodeling. Furthermore, there are data to suggest that infection, the microbiome, circulating microparticles, and the plasma metabolome are contributing to the pathobiology of CTEPH.

The article reviews current approaches to diagnosing and treating chronic thromboembolic pulmonary hypertension (CTEPH). The definition of the CTEPH is given, and its main risk factors are described. It is shown that the modern algorithm of diagnostic search includes four stages; the examination methods used at each stage are characterized. The most rational approach to CTEPH therapy is provided; the possibilities and limitations of pulmonary endarterectomy, transluminal balloon angioplasty of the pulmonary arteries, and specific therapy of pulmonary hypertension in such patients are described. The clinical presentation and treatment of CTEPH according to the Russian Pulmonary Hypertension Registry are reviewed.
В статье анализируются современные подходы к диагностике и лечению хронической тромбоэмболической легочной гипертензии (ХТЭЛГ). Приводится определение заболевания, описываются основные факторы риска развития ХТЭЛГ. Указывается, что, согласно современному алгоритму диагностического поиска, выделяются четыре его этапа, дается характеристика методам исследования, которые применяются на каждом из этапов. Суммируются представления о наиболее рациональном подходе к терапии ХТЭЛГ, описываются возможности и ограничения легочной эндартерэктомии, транслюминальной баллонной ангиопластики легочных артерий, специфическая терапия легочной артериальной гипертонии у этой категории пациентов. Приводятся данные об особенностях клиники и лечения ХТЭЛГ по данным Российского регистра легочной гипертензии.

Chronic thromboembolic pulmonary hypertension is rare, underdiagnosed form of pulmonary hypertension. It is caused by intravascular obstruction of pulmonary arteries due to fibrotic transformation of thromboembolic material and microvasculopathy. It is important to diagnose this variant as potentially curative treatment in the form of pulmonary endarterectomy is available. Last two decades have seen rapid advances in targeted medical management and refinement in balloon pulmonary angioplasty technique, which have provided a viable therapeutic option for patients who deemed to be inoperable.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high-output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left-sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.

Life-long anticoagulation is the recommended management for chronic thromboembolic pulmonary hypertension (CTEPH). Evidence regarding the use of direct oral anticoagulants (DOAC) for CTEPH is yet to be established. We performed a systematic review and meta-analysis to clarify the outcomes of CTEPH in patients who used DOAC or vitamin K antagonists (VKA).
We reviewed literature in PubMed and EMBASE through March 2023. We included studies involving patients with CTEPH where DOAC and VKA were compared. We collected data including intervention history for CTEPH, bleeding events, recurrence of VTE (venous thromboembolism), and mortality. We performed a meta-analysis using the Mantel-Haenszel method with a fixed-effects model.
We included one randomized clinical trial and six observational studies, with a total of 2969 patients. Six studies investigated major bleeding outcomes, and seven investigated all bleeding outcomes. There were no differences in major bleeding (RR 0.59, 95 % CI [0.34-1.02], I2 = 0 %) and all-bleeding (RR 0.87, 95 % CI [0.67-1.13], I2 = 0 %). Based on the five studies we included, DOAC was associated with a lower risk of mortality (RR 0.54, 95 % CI: 0.37-0.79, I2 = 5 %). However, a higher risk of recurrent pulmonary embolism (PE) was seen in three studies (RR 3.80, 95 % CI: [1.93-7.50], I2 = 11 %). No significant differences were noted in terms of VTE.
DOAC compared to VKA was associated with a significantly lower mortality and higher risk of recurrent PE. Since most of the included studies are observational, we must consider the existence of multiple biases and confounding factors.

Among five types of pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) is the only curable form, but prompt and accurate diagnosis can be challenging. Computed tomography and nuclear medicine-based techniques are standard imaging modalities to non-invasively diagnose CTEPH, however these are limited by radiation exposure, subjective qualitative bias, and lack of cardiac functional assessment. This review aims to assess the methodology, diagnostic accuracy of pulmonary perfusion imaging in the current literature and discuss its advantages, limitations and future research scope.

Introduction: Pulmonary endarterectomy (PEA) is known to be a curative intervention for chronic thromboembolic pulmonary hypertension (CTEPH). Its complications include endobronchial bleeding, persistent pulmonary arterial hypertension, right ventricular failure, and reperfusion lung injury. Extracorporeal membranous oxygenation (ECMO) is a perioperative salvage method for PEA. Although risk factors and outcomes have been reported in several studies, overall trends remain unknown. We performed a systematic review and study-level meta-analysis to understand the outcomes of ECMO utilization in the perioperative period of PEA. Methods: We performed a literature search with PubMed and EMBASE on 11/18/2022. We included studies including patients who underwent perioperative ECMO in PEA. We collected data including baseline demographics, hemodynamic measurements, and outcomes such as mortality and weaning of ECMO and performed a study-level meta-analysis. Results: Eleven studies with 2632 patients were included in our review. ECMO insertion rate was 8.7% (225/2,625, 95% CI 5.9-12.5) in total, VV-ECMO was performed as the initial intervention in 1.1% (41/2,625, 95% CI 0.4-1.7) (Figure 3), and VA-ECMO was performed as an initial intervention in 7.1% (184/2,625, 95% CI 4.7-9.9). Preoperative hemodynamic measurements showed higher pulmonary vascular resistance, mean pulmonary arterial pressure, and lower cardiac output in the ECMO group. Mortality rates were 2.8% (32/1238, 95% CI: 1.7-4.5) in the non-ECMO group and 43.5% (115/225, 95% CI: 30.8-56.2) in the ECMO group. The proportion of patients with successful weaning of ECMO was 72.6% (111/188, 95% CI: 53.4-91.7). Regarding complications of ECMO, the incidence of bleeding and multi-organ failure were 12.2% (16/79, 95% CI: 13.0-34.8) and 16.5% (15/99, 95% CI: 9.1-28.1), respectively. Conclusion: Our systematic review showed a higher baseline cardiopulmonary risk in patients with perioperative ECMO in PEA, and its insertion rate was 8.7%. Further studies that compare the use of ECMO in high-risk patients who undergo PEA are anticipated.

Main pulmonary vascular diseases (PVD) with precapillary pulmonary hypertension (PH) are pulmonary arterial and chronic thromboembolic PH. Guidelines recommend supplemental oxygen therapy (SOT) for severely hypoxemic patients with PH, but evidence is scarce. The authors performed a systematic review and where possible meta-analyses on the effects of SOT on hemodynamics and exercise performance in patients with PVD. In PVD, short-term SOT significantly improved mean pulmonary artery pressure and exercise performance. There is growing evidence on the benefit of long-term SOT for selected patients with PVD regarding exercise capacity and maybe even survival.