Publications
340 results found
Rothman A, Vachiery JE, Howard LS, et al., 2020, Percutaneous Endovascular Ultrasound Pulmonary Artery Denervation for the Treatment of Pulmonary Arterial Hypertension: 12-Month Results of the Trophy 1 Study, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Sitbon O, Howard L, 2019, Management of pulmonary arterial hypertension in patients aged over 65 years, European Heart Journal Supplements, Vol: 21, Pages: 29-36, ISSN: 1520-765X
Historically, pulmonary arterial hypertension (PAH) has been considered a disease of young adults, but over the last three decades, the average age at diagnosis has increased, presenting clinicians with some unique challenges. Clinical symptoms of PAH, including shortness of breath and reduced functional capacity, are not specific for the disease and may be present in older patients because of their age or as a result of comorbid conditions. Eliminating other causes for these symptoms can delay PAH diagnosis and initiation of PAH-specific treatment compared with younger patients. Currently, there are no specific guidelines relating to PAH in older patients and existing guidelines for identifying patients at potential risk of PAH may not be appropriate for patients aged over 65 years. Even though older patients tend to be diagnosed with more advanced symptoms, and evidence suggests that they are less responsive to PAH-specific therapies, treatment is often less aggressive than in younger patients. Even after adjusting for age, survival rates remain disproportionately lower in the older vs. younger PAH populations. Specific guidelines for diagnosis and treatment of older patients with PAH are needed to improve care and outcomes in this growing population. This review aims to assess the challenges associated with diagnosing and managing PAH in older patients, based on literature searches, authors’ experiences, and expert opinions.
Babu A, Ruggiero A, Cannon JE, et al., 2019, EVOLVING SURGICAL EXPERTISE AND PATIENT CHOICE IN PULMONARY ENDARTERECTOMY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A155-A156, ISSN: 0040-6376
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- Citations: 1
Bunclark K, Liley J, Newnham M, et al., 2019, MACHINE LEARNING TOOL PROVIDES NEW INSIGHTS INTO RISK ASSESSMENT IN PULMONARY ENDARTERECTOMY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A154-A155, ISSN: 0040-6376
Cogliano M, Lawrie A, Kiely DG, et al., 2019, Thoracic CT features of patients with BMPR2 mutation: preliminary analysis from the UK National Cohort Study of Idiopathic and Heritable PAH, International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Howard L, He J-G, Wharton J, et al., 2019, Late Breaking Abstract - Supplementation of iron in pulmonary hypertension (SIPHON): results from a randomised controlled crossover trial, European-Respiratory-Society (ERS) International Congress, Publisher: European Respiratory Society, Pages: 1-2, ISSN: 0903-1936
Background: Iron deficiency in the absence of anaemia is common in patients with idiopathic pulmonary arterial hypertension (IPAH). It has been associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis and correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown.Methods: Iron-deficient patients (defined as ferritin <37µg/L, serum iron <10.3µmol/L, transferrin saturation <16.4% or soluble transferrin receptor >28.1nmol/L) were randomised to receive a single infusion of ferric carboxymaltose (FCM) 15 mg/kg up to 1000mg or saline placebo with cross-over after 12 weeks of treatment. The primary outcome was change in endurance time on cardio-pulmonary exercise testing (CPET) at 12 weeks. Secondary measures included resting haemodynamics, incremental CPET, iron indices, 6 minute walk distance, WHO functional class, quality of life score, NT-proBNP and cardiac anatomy and function from MRI.Results: 40 patients enrolled and 39 provided data for analysis. FCM improved iron indices, with a significant increase in ferritin (P=0.0003) and reduction in soluble transferrin receptor levels (P<0.0001) at 12 weeks, and was well tolerated. There was no significant change in endurance time or in any other secondary endpoint. Data from a meta-analysis including a parallel study from Fuwai Hospital, China, will be available at the time of presentation.Conclusion: Iron repletion through a single infusion of FCM improves iron indices and is well tolerated but does not improve exercise capacity in PAH.
Su J, Hughes AD, Simonsen U, et al., 2019, Impact of pulmonary endarterectomy on pulmonary arterial wave propagation and reservoir function., Am J Physiol Heart Circ Physiol, Vol: 317, Pages: H505-H516
High wave speed and large wave reflection in the pulmonary artery have previously been reported in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We assessed the impact of pulmonary endarterectomy (PEA) on pulmonary arterial wave propagation and reservoir function in patients with CTEPH. Right heart catheterization was performed using a combined pressure and Doppler flow sensor-tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in eight patients with CTEPH before and 3 mo after PEA. Wave intensity and reservoir-excess pressure analyses were then performed. Following PEA, mean pulmonary arterial pressure (PAPm; ∼49 vs. ∼32 mmHg), pulmonary vascular resistance (PVR; ∼11.1 vs. ∼5.1 Wood units), and wave speed (∼16.5 vs. ∼8.1 m/s), i.e., local arterial stiffness, markedly decreased. The changes in the intensity of the reflected arterial wave and wave reflection index (pre: ∼28%; post: ∼22%) were small, and patients post-PEA with and without residual pulmonary hypertension (i.e., PAPm ≥ 25 mmHg) had similar wave reflection index (∼20 vs. ∼23%). The reservoir and excess pressure decreased post-PEA, and the changes were associated with improved right ventricular afterload, function, and size. In conclusion, although PVR and arterial stiffness decreased substantially following PEA, large wave reflection persisted, even in patients without residual pulmonary hypertension, indicating lack of improvement in vascular impedance mismatch. This may continue to affect the optimal ventriculoarterial interaction, and further studies are warranted to determine whether this contributes to persistent symptoms in some patients.NEW & NOTEWORTHY We performed wave intensity analysis in the pulmonary artery in patients with chronic thromboembolic pulmonary hypertension before and 3 mo after pulmonary endarterectomy. Despite substantial reduction in pulmonary arterial pres
Augustine DX, Coates-Bradshaw LD, Willis J, et al., 2019, Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography (vol 5, pg G11, 2018), ECHO RESEARCH AND PRACTICE, Vol: 6, Pages: X1-X1, ISSN: 2055-0464
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Howard L, 2019, Erratum: Acute pulmonary embolism., Clinical medicine (London, England), Vol: 19, Pages: 359-359, ISSN: 1470-2118
Wilson F, Saleem A, Coello C, et al., 2019, A novel approach to target validation in humans: Using positron emission tomography (PET) to evaluate the biodistribution of an FAK inhibitor in subjects with pulmonary arterial hypertension (PAH), British-Pharmacology-Society Meeting (Pharmacology), Publisher: WILEY, Pages: 1632-1632, ISSN: 0306-5251
Attard M, Dawes T, Simoes Monteiro de Marvao A, et al., 2019, Metabolic pathways associated with right ventricular adaptation to pulmonary hypertension: Three dimensional analysis of cardiac magnetic resonance imaging, EHJ Cardiovascular Imaging / European Heart Journal - Cardiovascular Imaging, Vol: 20, Pages: 668-676, ISSN: 2047-2412
AimsWe sought to identify metabolic pathways associated with right ventricular (RV) adaptation to pulmonary hypertension (PH). We evaluated candidate metabolites, previously associated with survival in pulmonary arterial hypertension, and used automated image segmentation and parametric mapping to model their relationship to adverse patterns of remodelling and wall stress.Methods and resultsIn 312 PH subjects (47.1% female, mean age 60.8 ± 15.9 years), of which 182 (50.5% female, mean age 58.6 ± 16.8 years) had metabolomics, we modelled the relationship between the RV phenotype, haemodynamic state, and metabolite levels. Atlas-based segmentation and co-registration of cardiac magnetic resonance imaging was used to create a quantitative 3D model of RV geometry and function—including maps of regional wall stress. Increasing mean pulmonary artery pressure was associated with hypertrophy of the basal free wall (β = 0.29) and reduced relative wall thickness (β = −0.38), indicative of eccentric remodelling. Wall stress was an independent predictor of all-cause mortality (hazard ratio = 1.27, P = 0.04). Six metabolites were significantly associated with elevated wall stress (β = 0.28–0.34) including increased levels of tRNA-specific modified nucleosides and fatty acid acylcarnitines, and decreased levels (β = −0.40) of sulfated androgen.ConclusionUsing computational image phenotyping, we identify metabolic profiles, reporting on energy metabolism and cellular stress-response, which are associated with adaptive RV mechanisms to PH.
Wei W, Tuna S, Keogh MJ, et al., 2019, Germline selection shapes human mitochondrial DNA diversity, Science, Vol: 364, ISSN: 0036-8075
INTRODUCTIONOnly 2.4% of the 16.5-kb mitochondrial DNA (mtDNA) genome shows homoplasmic variation at >1% frequency in humans. Migration patterns have contributed to geographic differences in the frequency of common genetic variants, but population genetic evidence indicates that selection shapes the evolving mtDNA phylogeny. The mechanism and timing of this process are not clear.Unlike the nuclear genome, mtDNA is maternally transmitted and there are many copies in each cell. Initially, a new genetic variant affects only a proportion of the mtDNA (heteroplasmy). During female germ cell development, a reduction in the amount of mtDNA per cell causes a “genetic bottleneck,” which leads to rapid segregation of mtDNA molecules and different levels of heteroplasmy between siblings. Although heteroplasmy is primarily governed by random genetic drift, there is evidence of selection occurring during this process in animals. Yet it has been difficult to demonstrate this convincingly in humans.RATIONALETo determine whether there is selection for or against heteroplasmic mtDNA variants during transmission, we studied 12,975 whole-genome sequences, including 1526 mother–offspring pairs of which 45.1% had heteroplasmy affecting >1% of mtDNA molecules. Harnessing both the mtDNA and nuclear genome sequences, we then determined whether the nuclear genetic background influenced mtDNA heteroplasmy, validating our findings in another 40,325 individuals.RESULTSPreviously unknown mtDNA variants were less likely to be inherited than known variants, in which the level of heteroplasmy tended to increase on transmission. Variants in the ribosomal RNA genes were less likely to be transmitted, whereas variants in the noncoding displacement (D)–loop were more likely to be transmitted. MtDNA variants predicted to affect the protein sequence tended to have lower heteroplasmy levels than synonymous variants. In 12,975 individuals, we identified a correlation between
Howard L, 2019, Acute pulmonary embolism, CLINICAL MEDICINE, Vol: 19, Pages: 243-247, ISSN: 1470-2118
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- Citations: 22
Gawecki F, Strangeways T, Amin A, et al., 2019, Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations, QJM: An International Journal of Medicine, Vol: 112, Pages: 335-342, ISSN: 1460-2393
Background: Pulmonary arteriovenous malformations (PAVMs) generate a right-to-left shunt. Impaired gas exchange results in hypoxemia and impaired CO2 clearance. Most patients compensate effectively but a proportion are dyspneic, and these are rarely the most hypoxaemic. Aim: To test degrees of concurrent pathology influencing exercise capacity. Design: Replicate, sequential single centre, prospective studies. Methods: Cardiopulmonary exercise tests (CPET) were performed in 26 patients with PAVMs, including individuals with and without known airflow obstruction. To replicate, relationships were tested prospectively in an independent cohort where self-reported exercise capacity evaluated by the Veterans Specific Activity Questionnaire (VSAQ) was used to calculate metabolic equivalents at peak exercise (METS N = 71). Additional measurements included oxygen saturation (SpO2), forced expiratory volume in 1 second (FEV1), vital capacity (VC), exhaled nitric oxide (FeNO), haemoglobin and iron indices. Results: By CPET, the peak work-rate was only minimally associated with low SpO2 or low arterial oxygen content (CaO2=1.34 x SpO2 x haemoglobin), but was reduced in patients with low FEV1 or VC. Supranormal work-rates were seen in patients with severe right-to-left shunting and SpO2 <90%, but only if FEV1 was >80% predicted. VSAQ-calculated METS also demonstrated little relationship with SpO2, and in crude and CaO2-adjusted regression, were lower in patients with lower FEV1 or VC. Bronchodilation increased airflow even where spirometry was in the normal range: exhaled nitric oxide measurements were normal in 80% of cases, and unrelated to any PAVM-specific variable. Conclusions: Exercise capacity is reduced by relatively mild airflow limitation (obstructive or restrictive) in the setting of PAVMs.
Di Scala L, Howard LS, Jing ZC, et al., 2019, MEDICAL THERAPY FOR CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION: AN INDIRECT TREATMENT COMPARISON OF MACITENTAN AND RIOCIGUAT, Publisher: ELSEVIER SCIENCE INC, Pages: S335-S335, ISSN: 1098-3015
Sofianopoulou E, Kaptoge S, Gräf S, et al., 2019, Traffic exposures, air pollution and outcomes in pulmonary arterial hypertension: A United Kingdom cohort study analysis., European Respiratory Journal, Vol: 53, Pages: 1-12, ISSN: 0903-1936
While traffic and air pollution exposure is associated with increased mortality in numerous diseases, its association with disease severity and outcomes in pulmonary arterial hypertension (PAH) remains unknown.Exposure to particulate matter ≤2.5 μm3 (PM2.5), nitrogen dioxide (NO2) and indirect measures of traffic-related air pollution (distance to main road and length of roads within buffer zones surrounding residential addresses) were estimated for 301 patients with idiopathic/heritable PAH recruited in the UK PAH national Cohort study. Associations with transplant-free survival and pulmonary hemodynamic severity at baseline were assessed, adjusting for confounding variables defined a priori.Higher estimated exposure to PM2.5 was associated with higher risk of death or lung transplant (Unadjusted hazard ratio (HR) 2.68; 95% CI 1.11-6.47 per 3 μg·m-3, p=0.028). This association remained similar when adjusted for potential confounding variables (HR 4.38; 95% CI 1.44-13.36 per 3 μg·m-3, p=0.009). No associations were found between NO2 exposure or other traffic pollution indicators and transplant-free survival Conversely, indirect measures of exposure to traffic-related air pollution within the 500-1000 m buffer zones correlated with the ERS/ESC risk categories as well as pulmonary hemodynamics at baseline. This association was strongest for pulmonary vascular resistance.In idiopathic/heritable PAH, indirect measures of exposure to traffic-related air pollution were associated with disease severity at baseline, whereas higher PM2.5 exposure may independently predict shorter transplant-free survival.
Newnham M, South K, Bleda M, et al., 2019, The ADAMTS13-VWF axis is dysregulated in chronic thromboembolic pulmonary hypertension, European Respiratory Journal, Vol: 53, ISSN: 0903-1936
Chronic thromboembolic pulmonary hypertension (CTEPH) is an important consequence of pulmonary embolism (PE) that is associated with abnormalities in haemostasis. We investigated the ADAMTS13-VWF axis in CTEPH, including its relationship to disease severity, inflammation, ABO groups and ADAMTS13 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 PE (n=28), idiopathic pulmonary arterial hypertension (n=30) and healthy controls (n=68). CTEPH genetic ABO associations and protein quantitative trait loci were investigated. ADAMTS-VWF axis abnormalities were assessed in CTEPH and healthy control subsets by measuring ADAMTS13 activity, D-dimers and VWF-multimeric size.CTEPH patients had decreased ADAMTS13 (adjusted β (95% CI)=−23.4 (−30.9– −15.1)%, p<0.001) and increased VWF levels (β=+75.5 (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 identify a genetic variant near the ADAMTS13 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.
Harbaum L, Ghataorhe P, Wharton J, et al., 2019, Reduced plasma levels of small HDL particles transporting fibrinolytic proteins in pulmonary arterial hypertension, Thorax, Vol: 74, Pages: 380-389, ISSN: 1468-3296
Background Aberrant lipoprotein metabolism has been implicated in experimental pulmonary hypertension, but the relevance to patients with pulmonary arterial hypertension (PAH) is inconclusive.Objective To investigate the relationship between circulating lipoprotein subclasses and survival in patients with PAH.Methods Using nuclear magnetic resonance spectroscopy, 105 discrete lipoproteins were measured in plasma samples from two cohorts of patients with idiopathic or heritable PAH. Data from 1124 plasma proteins were used to identify proteins linked to lipoprotein subclasses. The physical presence of proteins was confirmed in plasma lipoprotein subfractions separated by ultracentrifugation.Results Plasma levels of three lipoproteins from the small high-density lipoprotein (HDL) subclass, termed HDL-4, were inversely related to survival in both the discovery (n=127) and validation (n=77) cohorts, independent of exercise capacity, comorbidities, treatment, N-terminal probrain natriuretic peptide, C reactive protein and the principal lipoprotein classes. The small HDL subclass rich in apolipoprotein A-2 content (HDL-4-Apo A-2) exhibited the most significant association with survival. None of the other lipoprotein classes, including principal lipoprotein classes HDL and low-density lipoprotein cholesterol, were prognostic. Three out of nine proteins identified to associate with HDL-4-Apo A-2 are involved in the regulation of fibrinolysis, namely, the plasmin regulator, alpha-2-antiplasmin, and two major components of the kallikrein–kinin pathway (coagulation factor XI and prekallikrein), and their physical presence in the HDL-4 subfraction was confirmed.Conclusion Reduced plasma levels of small HDL particles transporting fibrinolytic proteins are associated with poor outcomes in patients with idiopathic and heritable PAH.
Grapsa I, Tan T, Nunes MDC, et al., 2019, IMPACT OF ADVERSE RIGHT VENTRICULAR REMODELING ON MORTALITY IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION, 68th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 1912-1912, ISSN: 0735-1097
Rhodes CJ, Batai K, Bleda M, et al., 2019, Genetic determinants of risk in pulmonary arterial hypertension: international case-control studies and meta-analysis, Lancet Respiratory Medicine, Vol: 7, Pages: 227-238, ISSN: 2213-2600
BackgroundRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.MethodsWe did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.FindingsA locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55–2·08], p=5·13 × 10–15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42–1·71], p=7·65 × 10–20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25–1·48], p=1·69 × 10–12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-media
Alikhan R, Lister S, Bomken C, et al., 2019, Apixaban Length-Of-Stay Pulmonary Embolism study - Hospital Admissions (ALPHA-PE), 59th Annual Scientific Meeting of the British-Society-for-Hematology, Publisher: WILEY, Pages: 139-140, ISSN: 0007-1048
Bello G, Dawes T, Duan J, et al., 2019, Deep learning cardiac motion analysis for human survival prediction, Nature Machine Intelligence, Vol: 1, Pages: 95-104, ISSN: 2522-5839
Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimizing the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimized for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients, the predictive accuracy (quantified by Harrell’s C-index) was significantly higher (P = 0.0012) for our model C = 0.75 (95% CI: 0.70–0.79) than the human benchmark of C = 0.59 (95% CI: 0.53–0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival.
McGoon MD, Ferrari P, Armstrong I, et al., 2019, The importance of patient perspectives in pulmonary hypertension, European Respiratory Journal, Vol: 53, ISSN: 0903-1936
The assessment of objective measurement of cardiopulmonary status has helped us achieve better clinical outcomes for patients and develop new therapies through to the point of market access; however, patient surveys indicate that more can be done to improve holistic care and patient engagement. In this multidisciplinary review, we examine how clinical teams can acknowledge and embrace the individual patient's perspective, and thus improve the care for individual patients suffering from pulmonary hypertension by cultivating the importance and relevance of health-related quality of life in direct clinical care. At the individual level, patients should be provided with access to accredited specialist centres which provide a multidisciplinary approach where there is a culture focused on narrative medicine, quality of life, shared decision making and timely access to palliative care, and where there is participation in education. On a larger scale, we call for the development, expansion and promotion of patient associations to support patients and carers, lobby for access to best care and treatments, and provide input into the development of clinical trials and registries, focusing on the patients' perspective.
Hemnes AR, Luther JM, Rhodes CJ, et al., 2019, Human PAH is characterized by a pattern of lipid-related insulin resistance, JCI Insight, Vol: 4, Pages: 1-13, ISSN: 2379-3708
BACKGROUND. Pulmonary arterial hypertension (PAH) is a deadly disease of the small pulmonary vasculature with an increased prevalence of insulin resistance (IR). Insulin regulates both glucose and lipid homeostasis. We sought to quantify glucose- and lipid-related IR in human PAH, testing the hypothesis that lipoprotein indices are more sensitive indices of IR in PAH.METHODS. Oral glucose tolerance testing in PAH patients and triglyceride-matched (TG-matched) controls and proteomic, metabolomics, and lipoprotein analyses were performed in PAH and controls. Results were validated in an external cohort and in explanted human PAH lungs.RESULTS. PAH patients were similarly glucose intolerant or IR by glucose homeostasis metrics compared with control patients when matched for the metabolic syndrome. Using the insulin-sensitive lipoprotein index, TG/HDL ratio, PAH patients were more commonly IR than controls. Proteomic and metabolomic analysis demonstrated separation between PAH and controls, driven by differences in lipid species. We observed a significant increase in long-chain acylcarnitines, phosphatidylcholines, insulin metabolism–related proteins, and in oxidized LDL receptor 1 (OLR1) in PAH plasma in both a discovery and validation cohort. PAH patients had higher lipoprotein axis–related IR and lipoprotein-based inflammation scores compared with controls. PAH patient lung tissue showed enhanced OLR1 immunostaining within plexiform lesions and oxidized LDL accumulation within macrophages.CONCLUSIONS. IR in PAH is characterized by alterations in lipid and lipoprotein homeostasis axes, manifest by elevated TG/HDL ratio, and elevated circulating medium- and long-chain acylcarnitines and lipoproteins. Oxidized LDL and its receptor OLR1 may play a role in a proinflammatory phenotype in PAH.FUNDING. NIH DK096994, HL060906, UL1 RR024975-01, UL1 TR000445-06, DK020593, P01 HL108800-01A1, and UL1 TR002243; American Heart Association 13FTF16070002.
Howard LS, Ghofrani HA, D'Armini AM, et al., 2019, Long-Term Safety, Tolerability and Efficacy of Macitentan in Patients with Inoperable Chronic Thromboembolic Pulmonary Hypertension: The MERIT-1 Study and Its Open-Label Extension MERIT-2, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
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Dimopoulos K, Condliffe R, Tulloh RMR, et al., 2018, Echocardiographic Screening for Pulmonary Hypertension in Congenital Heart Disease <i>JACC</i> Review Topic of the Week, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 72, Pages: 2778-2788, ISSN: 0735-1097
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Swietlik EM, Hodgson J, Hadinnapola C, et al., 2018, PHENOTYPIC CHARACTERISATION OF GDF2 MUTATION CARRIERS IN A LARGE COHORT OF PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A24-A26, ISSN: 0040-6376
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Gawecki F, Tighe HC, Perks J, et al., 2018, THE VETERANS SPECIFIC ACTIVITY QUESTIONNAIRE (VSAQ) AS A NEW AND EFFECTIVE METHOD OF ASSESSING EXERCISE CAPACITY IN PATIENTS WITH PULMONARY ARTERIOVENOUS MALFORMATIONS (PAVMS), Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A103-A103, ISSN: 0040-6376
Thurairatnam S, Santhirapala V, Strangeways T, et al., 2018, THE ROLE OF CARDIOPULMONARY EXERCISE TESTING IN ASSESSING ANAESTHETIC RISK FACTORS IN PATIENTS WITH PULMONARY ARTERIOVENOUS MALFORMATIONS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A103-A104, ISSN: 0040-6376
Gruenig E, Eichstaedt C, Barbera J-A, et al., 2018, ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension, EUROPEAN RESPIRATORY JOURNAL, Vol: 53, ISSN: 0903-1936
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