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In chronic thromboembolic pulmonary hypertension (CTEPH), stenoses or obstructions of the pulmonary arteries due to organized thrombi can cause an elevation in pulmonary artery resistance, which in turn can result in pulmonary hypertension and progressive right heart failure. CTEPH can be cured surgically by pulmonary endarterectomy (PEA); however, patients deemed unsuitable for PEA due to distal lesion, advanced age, or comorbidities have a poor prognosis and limited treatment options. Recently, an alternative interventional strategy of balloon pulmonary angioplasty (BPA) reduces pulmonary artery hypertension in patients with CTEPH. Risk/benefit inbalance appear to be safe in experimented center. BPA can treat the lesions from lobar to subsegmental pulmonary arteries, improving functional and hemodynamic status for inoperable patients. This review highlights this recent progress., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: The development of pulmonary hypertension (PH) has multifactorial underlying pathophysiological causes and can be classified into five groups. While three different classes of therapeutic drugs are licensed for the treatment of pulmonary arterial hypertension (PAH, WHO group 1), specific medical therapies are lacking for other forms of PH, such as PH due to left heart disease. In 2013 riociguat, a first-in class soluble guanylate cyclase stimulator, has also become available for the treatment of PAH. Riociguat was further introduced as the first approved pharmacotherapy for the treatment of patients with chronic thromboembolic PH (WHO group 4, CTEPH). Despite these advances in therapeutic options for patients with PH, none of these agents have been approved for the treatment of PH due to left heart disease. Areas covered: We aim to give an overview of the pathophysiology of PH, pharmacodynamics and pharmacokinetic properties, safety and efficacy of riociguat, including adverse events, contraindications and drug interactions. Expert opinion: Considering the increasingly broad indications for riociguat in patients with PH, substantial knowledge of data and properties on safety and efficacy of riociguat are becoming more and more important for physicians prescribing riociguat to PH patients.

Pulmonary thromboendarterectomy (PTE), also referred to as pulmonary endarterectomy, is the definitive treatment for chronic thromboembolic pulmonary hypertension (CTEPH). The true incidence of CTEPH is unknown and difficult to ascertain; however, most experts agree that approximately 4% to 5% of all patients who have an acute episode of pulmonary embolism (PE) will continue to develop CTEPH. Based on an incidence rate of about 0.1% for acute PE, this translates into a CTEPH incidence of approximately 10,000 to 15,000 annually in the United States alone. Furthermore, there are patients with CTEPH who have no history of prior PE or deep vein thrombosis, adding to the estimated number. Despite these facts, the disease remains significantly underdiagnosed, and currently there are only about 300 PTEs performed nationwide, the majority of which are done at the University of California, San Diego (UCSD) Health System. The technical aspects of the procedure can be somewhat challenging and require meticulous and complete dissection of the entire pulmonary vascular tree, with the patient under profound hypothermic circulatory arrest. However, the determination of true CTEPH patients and those who would benefit from surgery can also be challenging and relies heavily on the experience of the CTEPH team. In this article, we will highlight some key points about the disease and describe the surgical techniques of PTE.

Pulmonary endarterectomy is a curative treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). There is a growing body of evidence suggesting that not only patients with CTEPH but also patients with pulmonary arterial obstructions and mean pulmonary artery pressures < 25 mmHg should be offered surgery. In this review, the recent literature regarding pathophysiology, diagnostic methods, decision making by an expert CTEPH team, and surgical techniques will be summarized. Novel alternative treatment options for inoperable CTEPH patients will be discussed, i.e. targeted medical therapy and balloon pulmonary angioplasty. For the future the major task will be to define a clear selection process for the optimal treatment of the individual CTEPH patient.

Background: The purpose of the study was to examine pulmonary hypertension (PH) patients' quality of life (QOL) for the first time in Finland., Methods: This was a non-interventional, cross-sectional study. The SF-36v2 questionnaire was sent to the PH patients who had been referred to or followed up on at the Helsinki University Central Hospital's pulmonary clinic for idiopathic pulmonary arterial hypertension, associated pulmonary arterial hypertension (APAH), or chronic thromboembolic PH (CTEPH). The patients were on pulmonary arterial hypertension (PAH) - specific drugs, were at least 18 years old, and had signed an informed consent., Results: There were 62 patients who fulfilled the inclusion criteria, and 53% of respondents rated their health as moderate. Similarly, 55% of respondents rated their health status approximately the same compared to their situation 1 year ago. QOL was impaired in all other subscales, except for the mental health and mental component score. A majority of patients suffered from PH symptoms, which worsened their QOL. The greatest impact on their QOL was associated with a high World Health Organization (WHO) functional class (FC), poor performance in a 6-min walking test (6MWT), symptoms, oxygen therapy, elevated pro-brain natriuretic peptide, pericardial effusion, APAH etiology, and being retired from work., Conclusions: The respondents had a reduced QOL, compared to the general population, in all other subscales, except for mental health. APAH patients had the worst QOL. Good results in functional capacity measures (WHO FC, 6MWT) were associated with a better QOL. Patients' QOL can be improved by reducing the symptoms of PAH.

Registries of patients with pulmonary arterial hypertension (PAH) have been instrumental in characterizing the presentation and natural history of the disease and provide a basis for prognostication. Since the initial accumulation of data conducted in the 1980s, subsequent registry databases have yielded information about the demographic factors, treatment, and survival of patients and have permitted comparisons between populations in different eras and environments. Inclusion of patients with all subtypes of PAH has also allowed comparisons of these subpopulations. We describe herein the basic methodology by which PAH registries have been conducted, review key insights provided by registries, summarize issues related to interpretation and comparison of the results, and discuss the utility of data to predict survival outcomes. Potential sources of bias, particularly related to the inclusion of incident and/or prevalent patients and missing data, are addressed. A fundamental observation of current registries is that survival in the modern treatment era has improved compared with that observed previously and that outcomes among PAH subpopulations vary substantially. Continuing systematic clinical surveillance of PAH will be important as treatment evolves and as understanding of mechanisms advance. Considerations for future directions of registry studies include enrollment of a broader population of patients with pulmonary hypertension of all clinical types and severity and continued globalization and collaboration of registry databases., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Since the last World Symposium on Pulmonary Hypertension in 2008, we have witnessed numerous and exciting developments in chronic thromboembolic pulmonary hypertension (CTEPH). Emerging clinical data and advances in technology have led to reinforcing and updated guidance on diagnostic approaches to pulmonary hypertension, guidelines that we hope will lead to better recognition and more timely diagnosis of CTEPH. We have new data on treatment practices across international boundaries as well as long-term outcomes for CTEPH patients treated with or without pulmonary endarterectomy. Furthermore, we have expanded data on alternative treatment options for select CTEPH patients, including data from multiple clinical trials of medical therapy, including 1 recent pivotal trial, and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have garnered more experience, and on a larger international scale, with pulmonary endarterectomy, which is the treatment of choice for operable CTEPH. This report overviews and highlights these important interval developments as deliberated among our task force of CTEPH experts and presented at the 2013 World Symposium on Pulmonary Hypertension in Nice, France., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Venous thromboembolism comprises deep-vein thrombosis, thrombus in transit, acute pulmonary embolism, and chronic thromboembolic pulmonary hypertension (CTEPH). Pulmonary thromboemboli commonly resolve, with restoration of normal pulmonary hemodynamics. When they fail to resorb, permanent occlusion of the deep veins and/or CTEPH are the consequences. Apart from endogenous fibrinolysis, venous thrombi resolve by a process of mechanical fragmentation, through organization of the thromboembolus by invasion of endothelial cells, leukocytes, and fibroblasts leading to recanalization. Recent data utilizing various models have contributed to a better understanding of venous thrombosis and the resolution process that is directed at maintaining vascular patency. This review summarizes the plasmatic and cellular components of venous thrombus formation and resolution.

Introduction: Although quality of life (QoL) is recognized as an important indicator of the course of a disease, it has rarely been addressed in studies evaluating the outcome of care for patients with pulmonary embolism (PE). This study primarily aimed to evaluate the QoL of patients with acute PE in comparison to population norms and to patients with other cardiopulmonary diseases, using a generic QoL questionnaire. Secondary, the impact of time period from diagnosis and clinical patient characteristics on QoL was assessed, using a disease-specific questionnaire., Methods: QoL was assessed in 109 consecutive out-patients with a history of objectively confirmed acute PE (mean age 60.4 ± 15.0 years, 56 females), using the generic Short Form-36 (SF-36) and the disease specific Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL). The score of the SF-36 were compared with scores of the general Dutch population and reference populations with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), a history of acute myocardial infarction (AMI), derived from the literature. Scores on the SF-35 and PEmb-QoL were used to evaluate QoL in the short-term and long-term clinical course of patients with acute PE. In addition, we examined correlations between PEmb-QoL scores and clinical patient characteristics., Results: Compared to scores of the general Dutch population, scores of PE patients were worse on several subscales of the SF-36 (social functioning, role emotional, general health (P<0.001), role physical and vitality (P<0.05)). Compared to patients with COPD and CHF, patients with PE scored higher (=better) on all subscales of the SF-36 (P ≤ 0.004) and had scores comparable with patients with AMI the previous year. Comparing intermediately assessed QoL with QoL assessed in long-term follow-up, PE patients scored worse on SF-36 subscales: physical functioning, social functioning, vitality (P<0.05), and on the PEmb-QoL subscales: emotional complaints and limitations in ADL (P ≤ 0.03). Clinical characteristics did not correlate with QoL as measured by PEmb-QoL., Conclusion: Our study demonstrated an impaired QoL in patients after treatment of PE. The results of this study provided more knowledge about QoL in patients treated for PE., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Right-sided cardiac masses are infrequent and have varied clinical presentation. The present study describes the clinical features, echocardiographic findings and management of 19 patients presenting with right-sided cardiac thrombi in a tertiary care center in north India., Methods: This is a retrospective, single center observational study of consecutive patients over the period January 2003-2008 admitted in our emergency intensive care unit (EICU). We identified 38 patients with right-sided cardiac masses admitted to EICU diagnosed by transthoracic echocardiography of which 19 patients had right-sided thrombus. The echocardiographic findings were reviewed by two cardiologists in all patients. Treatment was not standardized and choice of therapy was based on judgment of attending physician., Results: The mean age of patients with cardiac thrombus was 36.6 ± 11.8 years. Right atrial (n = 17) and right ventricle (n = 2) thrombi were associated with deep vein thrombosis (DVT) in 7 (36.8%) and pulmonary embolism in 3 (15%) patients. 13 (68.4%) patients appeared to have in situ mural thrombus. 12 patients were managed with oral anticoagulants, 3 patients underwent surgery and 4 patients were thrombolysed. All the survivors had a mean follow-up of 40 ± 6 months (range--18-50 months)., Conclusions: Prompt echocardiographic examination in an appropriate clinical setting facilitates faster diagnosis and management of patients with right-sided cardiac thrombi. High incidence of in situ mural thrombus and varied comorbidities predisposing to right-sided cardiac thrombi besides DVT and pulmonary embolism need to be recognized. Oral anticoagulation and thrombolysis appear to be the mainstay of treatment with surgery limited for selected patients., (Copyright © 2013. Published by Elsevier B.V.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by non-resolving thromboembolisms of the pulmonary arteries. In Japan, in contrast to Western countries, CTEPH is more prevalent in women. A Japanese multicenter study reported that a form of CTEPH unrelated to deep vein thrombosis is associated with HLA-B⁎5201, suggesting that this form of CTEPH may be associated with vasculopathy. CTEPH can be cured by pulmonary endarterectomy, provided that the thrombi are surgically accessible; thus, early diagnosis is important, and all patients with exertional dyspnea should be evaluated for pulmonary hypertension. Ventilation/perfusion scans provide an excellent non-invasive means to distinguish CTEPH from pulmonary arterial hypertension. Similarly, computed tomographic pulmonary angiograms allow for the detection of thrombi and evaluation of pulmonary hemodynamics in a minimally invasive manner. Importantly, the absence of subpleural perfusion on pulmonary angiograms can suggest the presence of small vessel disease. Small vessel disease might be involved in the pathogenesis of CTEPH, and its detection is essential in preventing operative death. Although no modern therapies for pulmonary arterial hypertension have been approved for treatment of CTEPH, a recent randomized control trial of riociguat in patients with CTEPH demonstrated that riociguat significantly improved 6-min walking distance. Further investigations into treatments that target endothelial dysfunction and hyperproliferative CTEPH cells are needed. Recently, balloon pulmonary angioplasty has emerged as a promising treatment modality in Japan. A specialized medical team, including at least one expert surgeon, should make decisions regarding patients' candidacy for pulmonary endarterectomy and/or balloon pulmonary angioplasty., (© 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objectives: This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure., Background: Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted., Methods: We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed., Results: Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p < 0.0001). Receiver-operating characteristic curve analysis demonstrated PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%)., Conclusions: Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Mechanisms contributing to the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) are poorly understood. This disorder is characterized by incomplete resolution of pulmonary perfusion defects resulting from acute venous thromboembolism. We previously identified several dysfibrinogenemias in some patients with CTEPH. The purpose of this study was to determine whether fibrin clot architecture might be implicated in the thrombolytic resistance in patients with these CTEPH-associated dysfibrinogenemias., Materials and Methods: Purified fibrinogen from patients and healthy controls was clotted with thrombin in the presence of calcium. Clot turbidity, porosity, and susceptibility to fibrinolysis were evaluated by spectrophotometric and permeation analyses. Fibrin network structure was assessed by laser-scanning confocal microscopy., Results: Compared to normal fibrinogen, CTEPH-associated dysfibrinogenemias exhibited low clot turbidity, decreased porosity, and fibrinolytic resistance. In addition, the dysfibrinogenemias exhibited a more disorganized fibrin network structure characterized by thinner fibers, greater network dispersal and more extensive fiber branching., Conclusions: Abnormal clot architecture and fibrinolytic resistance may contribute to incomplete clot resolution following acute venous thromboembolism in patients with CTEPH-associated dyfibrinogenemia., (© 2013. Published by Elsevier Ltd. All rights reserved.)

Introduction: Persistent obstruction in the pulmonary artery following acute pulmonary embolism (PE) can give rise to both chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease without PH (CTED). We hypothesised that cardiopulmonary exercise testing (CPET) may be able to differentiate patients with CTEPH and CTED following unresolved PE which may help guide patient assessment., Materials and Methods: Fifteen patients with CTEPH and 15 with CTED all diagnosed after PE underwent CT pulmonary angiography, CPET and resting right heart catheterisation. Exercise variables were compared between patients with CTEPH, CTED and 10 sedentary controls and analysed as predictors of a CTEPH diagnosis. Proximal thrombotic burden in CTEPH and CTED was quantified using CT criteria., Results: Physiological dead space (Vd/Vt) (34.5±11.4 vs 50.8±6.6 %, p<0.001) and alveolar-arterial oxygen gradient (29±16 vs 46±12mmHg, p <0.001) at peak exercise strongly differentiated CTED and CTEPH groups respectively. Resting ventilatory efficiency also differed from control subjects. In both univariate and multivariate analyses, peak exercise Vd/Vt predicted a diagnosis of CTEPH (ROC AUC>0.88, 0.67 - 0.97) despite a similar degree of proximal thrombotic obstruction to the CTED group (67.5, 55 - 70% and 72.5, 60 - 80% respectively, p=0.08)., Conclusions: Gas exchange at peak exercise differentiates CTED and CTEPH after PE that can present with no apparent relation to the degree of proximal thrombotic burden. A potential role for CPET exists in guiding further clinical investigations in this setting., (© 2013.)