Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism that is associated with abnormalities in haemostasis. We investigated the ADAMTS13-von ...Willebrand factor (VWF) axis in CTEPH, including its relationship with disease severity, inflammation,
groups and
genetic variants.ADAMTS13 and VWF plasma antigen levels were measured in patients with CTEPH (n=208), chronic thromboembolic disease without pulmonary hypertension (CTED) (n=35), resolved pulmonary embolism (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68). CTEPH genetic
associations and protein quantitative trait loci were investigated. ADAMTS13-VWF axis abnormalities were assessed in CTEPH and healthy control subsets by measuring ADAMTS13 activity, D-dimers and VWF multimeric size.Patients with CTEPH had decreased ADAMTS13 (adjusted β -23.4%, 95% CI -30.9- -15.1%, p<0.001) and increased VWF levels (β +75.5%, 95% CI 44.8-113%, p<0.001) compared to healthy controls. ADAMTS13 levels remained low after reversal of pulmonary hypertension by pulmonary endarterectomy surgery and were equally reduced in CTED. We identified a genetic variant near the
gene associated with ADAMTS13 protein that accounted for ∼8% of the variation in levels.The ADAMTS13-VWF axis is dysregulated in CTEPH. This is unrelated to pulmonary hypertension, disease severity or markers of systemic inflammation and implicates the ADAMTS13-VWF axis in CTEPH pathobiology.
Autoimmunity is believed to play a role in idiopathic pulmonary arterial hypertension (IPAH). It is not clear whether this is causative or a bystander of disease and if it carries any prognostic or ...treatment significance.
To study autoimmunity in IPAH using a large cross-sectional cohort.
Assessment of the circulating immune cell phenotype was undertaken using flow cytometry, and the profile of serum immunoglobulins was generated using a standardized multiplex array of 19 clinically validated autoantibodies in 473 cases and 946 control subjects. Additional glutathione S-transferase fusion array and ELISA data were used to identify a serum autoantibody to BMPR2 (bone morphogenetic protein receptor type 2). Clustering analyses and clinical correlations were used to determine associations between immunogenicity and clinical outcomes.
Flow cytometric immune profiling demonstrates that IPAH is associated with an altered humoral immune response in addition to raised IgG3. Multiplexed autoantibodies were significantly raised in IPAH, and clustering demonstrated three distinct clusters: "high autoantibody," "low autoantibody," and a small "intermediate" cluster exhibiting high concentrations of ribonucleic protein complex. The high-autoantibody cluster had worse hemodynamics but improved survival. A small subset of patients demonstrated immunoglobulin reactivity to BMPR2.
This study establishes aberrant immune regulation and presence of autoantibodies as key features in the profile of a significant proportion of patients with IPAH and is associated with clinical outcomes.
Isolated pulmonary artery involvement by large vessel vasculitis is rare. This case report describes two patients with large vessel pulmonary vasculitis initially thought to have chronic ...thromboembolic pulmonary hypertension who had their diagnosis revised following pulmonary endarterectomy surgery. Advances in imaging techniques such as positron emission tomography and magnetic resonance imaging have permitted complementary radiological methods of diagnosis and follow up of large vessel disease and these are discussed in conjunction with the immunosuppressive and operative management of these patients.
This investigation validated the inert gas rebreathing (IGR) technique and determined IGR prognostic ability compared to invasive cardiac output measurements in patients with pulmonary hypertension. ...IGR compared with thermodilution cardiac output demonstrated a moderate bias. IGR technique demonstrated long-term prognostic value comparable to invasive cardiac output in pulmonary hypertension patients
OBJECTIVES
Advanced age is not a barrier to cardiac surgery, with reports demonstrating excellent outcomes, but the effect of age on more complex surgery has not been studied. We assessed the ...outcomes of pulmonary endarterectomy (PEA) surgery in patients aged >70.
METHODS
A retrospective review of consecutive patients who underwent PEA between January 2006 and March 2011 at a national referral centre. The total cohort was dichotomized according to age on the day of surgery, either below or above 70 years. Outcomes were in-hospital mortality, overall survival and the length of ICU and hospital stays.
RESULTS
Four hundred and eleven patients underwent PEA during the 5-year period. The mean age was 56.9 years (range, 17-84 years). The in-hospital mortality was 14 of 308 (4.6%) for patients <70 years compared with 8 of 103 (7.8%) for patients ≥70 years (P = 0.21). The overall survival at 1, 2 and 3 years was 91.4, 89.9 and 87.7% in the <70-year old group and 85.9, 84.1 and 84.1% in the >70-year old group (log-rank test, P = 0.07), respectively. The length of ICU and in-hospital stays was longer in the >70-year old group, by 1 and 2 days, respectively (P = 0.005 and 0.001).
CONCLUSIONS
PEA surgery in patients ≥70 years is safe and carries a comparable risk of early mortality in younger patients, but there is an increase in resource use due to longer ICU and hospital stays. Advanced age should be taken into consideration when assessing suitability for PEA, but age per se should not be a contraindication to surgery.
Pulmonary hypertension is defined by physiological parameters but there are numerous causes that differ in their pathogenesis, management and prognosis. Causes include chronic cardiac or pulmonary ...diseases and diffuse small vessel disease but also a range of large vessel obstructive diseases. The physiological manifestation of all these diseases is increased pulmonary vascular resistance and pulmonary arterial hypertension, and while clinical features may provide a clue to diagnosis, imaging plays a fundamental role in establishing a precise diagnosis and therefore guiding therapy. Chronic thromboembolic pulmonary hypertension (CTEPH) is the most common large vessel cause of pulmonary hypertension. It is increasingly recognised as a major cause of morbidity and mortality which is underdiagnosed and often diagnosed late. The importance of CTEPH is that for patients in whom the distribution of disease lies predominantly in the proximal vasculature there is potential for symptomatic and physiological cure by surgical pulmonary endarterectomy. More distal disease may be suitable for medical management. Increased awareness on behalf of both clinicians and imagers is therefore paramount. However, there are other rare causes or large vessel obstruction/stenosis such as large vessel vasculitis, pulmonary artery tumour, fibrosing mediastinitis, congenital stenosis or extrinsic compression of the pulmonary arteries/veins. Atypical imaging appearance such as unilateral central pulmonary artery obstruction should lead to consideration of a diagnosis other than CTEPH.
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