Pulmonary arterial hypertension (PAH) is a debilitating disease that pervades all aspects of a patient's daily life. It is also increasingly acknowledged that the burden of PAH extends to older ...patients and carers. Until recently, the adverse effect of disease symptoms on the physical, emotional and social factors governing patient health-related quality of life (HRQoL) remained largely unrecognised. With a shift in therapeutic objectives to longer term improvements and HRQoL benefits, clinical trials now frequently include HRQoL measures as study end-points. Most HRQoL instruments used in patients with PAH are generic or non-disease-specific questionnaires and therefore may not accurately capture PAH disease burden. New PAH-specific HRQoL instruments currently undergoing validation include emPHasis-10 and Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT; Actelion Pharmaceuticals Ltd, Allschwil, Switzerland). Using various HRQoL measures, pharmacological therapies have been shown to improve HRQoL in patients with PAH. Patients also derive HRQoL benefits from nonpharmacological strategies, which include the emotional support provided by multidisciplinary care and support groups that is fundamental to patient wellbeing. Looking to the future, validated PAH-specific HRQoL instruments together with dedicated guidelines and procedures are essential to support the translation of HRQoL scores to the clinic, thus enabling a holistic treatment approach to the management of patients with PAH.
The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate- and high-risk strata are ...defined by estimated 1-year mortality risks of <5%, 5-10% and >10%, respectively. This risk assessment strategy awaits validation.We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation.Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata (p<0.001 for all comparisons). In the entire patient population, the observed mortality rates 1 year after diagnosis were 2.8% in the low-risk cohort (n=196), 9.9% in the intermediate-risk cohort (n=1116) and 21.2% in the high-risk cohort (n=276). In addition, the risk assessment strategy proved valid at follow-up and in major PAH subgroups.An abbreviated version of the risk assessment strategy proposed by the current European PH guidelines provides accurate mortality estimates in patients with PAH.
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.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism. As for most rare diseases, epidemiologic data are scarce, but recent registries suggest an ...incidence of at least 5 per million inhabitants per year. A history of massive or recurrent acute pulmonary embolism is observed in most patients with CTEPH, but the proportion of patients who develop CTEPH after acute pulmonary embolism is a matter of debate, further complicated by the possible misdiagnosis of CTEPH as acute pulmonary embolism. A complete resolution of thrombi is usually not achieved after acute pulmonary embolism, and the clinical relevance of a "postpulmonary embolism syndrome" with persistent perfusion defects and exercise intolerance is discussed. Risk factors most consistently associated with CTEPH are circulating anti-phospholipid antibodies or lupus anticoagulant, increased factor VIII, non-O blood groups, and chronic inflammatory diseases. There is no female predominance, and it is a disease of older age. Survival in the absence of specific surgical or medical treatment is poor and depends on the hemodynamic severity.
Chronic Thromboembolic Pulmonary Hypertension Kim, Nick H., MD; Delcroix, Marion, MD; Jenkins, David P., MB BS ...
Journal of the American College of Cardiology,
12/2013, Volume:
62, Issue:
25
Journal Article, Conference Proceeding
Peer reviewed
Open access
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.
Deficient angiogenesis and systemic inflammation could be involved in the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to characterise the histopathology of ...pulmonary vascular lesions from 52 CTEPH patients who underwent a pulmonary endarterectomy (PEA) and investigate a potential link between clinical, biological and morphometric parameters.Collagen, elastin, fibrin, lipid, endothelial, smooth muscle and inflammatory cell content was investigated using immunohistochemistry. Qualitative changes were evaluated using severity scores. Circulating levels of inflammatory mediators were measured using ELISA.Neointima, thrombotic, recanalised and atherosclerotic lesions were found. Accumulation of macrophages, T-lymphocytes and neutrophils was found mainly in atherosclerotic and thrombotic lesions. Angiogenesis was observed in all kinds of lesions; low-scored angiogenesis predicted adverse outcome, including persistent pulmonary hypertension post-PEA, start of medical therapy and poor survival. C-reactive protein (CRP), interleukin-10, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and matrix metalloproteinase (MMP)-9 were significantly elevated in CTEPH patients. Plasma CRP and MMP-9 levels correlated with neutrophil and macrophage accumulation, respectively.Enhanced systemic inflammation parallels local inflammatory cell infiltration in major pulmonary arteries at advanced stages of CTEPH. Impaired neovascularisation is associated with poor survival, start of medical treatment and persistent pulmonary hypertension post-PEA. These findings suggest that inflammation and impaired angiogenesis could contribute to the progression of the disease.
Chronic thromboembolic pulmonary hypertension (CTEPH) is the only potentially curable form of pulmonary hypertension. Rapid and accurate diagnosis is pivotal for successful treatment. Clinical signs ...and symptoms can be nonspecific and risk factors such as history of venous thromboembolism may not always be present. Echocardiography is the recommended first diagnostic step. Cardiopulmonary exercise testing is a complementary tool that can help to identify patients with milder abnormalities and chronic thromboembolic disease, triggering the need for further investigation. Ventilation/perfusion (
'/
') scintigraphy is the imaging methodology of choice to exclude CTEPH. Single photon emission computed tomography
'/
' is gaining popularity over planar imaging. Assessment of pulmonary haemodynamics by right heart catheterisation is mandatory, although there is increasing interest in noninvasive haemodynamic evaluation. Despite the status of digital subtraction angiography as the gold standard, techniques such as computed tomography (CT) and magnetic resonance imaging are increasingly used for characterising the pulmonary vasculature and assessment of operability. Promising new tools include dual-energy CT, combination of rotational angiography and cone beam CT, and positron emission tomography. These innovative procedures not only minimise misdiagnosis, but also provide additional vascular information relevant to treatment planning. Further research is needed to determine how these modalities will fit into the diagnostic algorithm for CTEPH.
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