Publications
393 results found
Hadinnapola C, Bleda M, Haimel M, et al., 2016, Utility Of Deep Phenotyping In The Identification And Validation Of Novel Causal Whole Genome Sequencing Variation In Patients With Pulmonary Arterial Hypertension, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Graf S, Bleda M, Hadinnapola C, et al., 2016, Whole Genome Sequencing In Idiopathic And Heritable Pulmonary Arterial Hypertension, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Price LC, Wort SJ, 2016, Pathophysiology and Causes of Pulmonary Hypertension, Oxford Textbook of Intensive Care Medicine
• Pulmonary hypertension (PH) in the critically ill may reflect an acute cause and/or an exacerbation of pre-existing PH, and is probably under-diagnosed.• The presence of right ventricular (RV) dysfunction and failure is an adverse prognostic feature. Associated PH crises and severe RV failure may progress rapidly to cardiovascular collapse. This is especially the case in RV ‘afterload mismatch’, when a normal RV is exposed to a sudden increase in afterload, such as following a massive pulmonary embolism (PE) or after lung transplantation.• Acute de novo causes of PH include those relating to post-capillary PH (e.g. left ventricular disease), acute lung injury, sepsis, and acute PE. Post-operative PH is not an infrequent problem and has many contributing factors.• Patients with pre-existing (‘chronic’) pulmonary arterial hypertension may require intensive care unit (ICU) management to manage severe RV failure (due to disease progression, intercurrent illness, or post-operatively). This is a very high-risk patient group with an ICU mortality of up to 50%.• Several general physiological challenges in the critical care environment are recognized to increase pulmonary vascular resistance and/or worsen RV function, including the effects of positive-pressure ventilation, hypoxaemia, and acidosis. In patients with PH, these should, if possible, be minimized
Treacy C, Blenda M, Hadinnapola C, et al., 2016, The Uk National Cohort Study Of Idiopathic And Heritable Pulmonary Arterial Hypertension, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
- Author Web Link
- Cite
- Citations: 2
Jensen AS, Broberg CS, Rydman R, et al., 2015, Impaired Right, Left, or Biventricular Function and Resting Oxygen Saturation Are Associated With Mortality in Eisenmenger Syndrome: A Clinical and Cardiovascular Magnetic Resonance Study., Circulation: Cardiovascular Imaging, Vol: 8, ISSN: 1941-9651
BACKGROUND: Patients with Eisenmenger syndrome (ES) have better survival, despite similar pulmonary vascular pathology, compared with other patients with pulmonary arterial hypertension. Cardiovascular magnetic resonance (CMR) is useful for risk stratification in idiopathic pulmonary arterial hypertension, whereas it has not been evaluated in ES. We studied CMR together with other noninvasive measurements in ES to evaluate its potential role as a noninvasive risk stratification test. METHODS AND RESULTS: Between 2003 and 2005, 48 patients with ES, all with a post-tricuspid shunt, were enrolled in a prospective, longitudinal, single-center study. All patients underwent a standardized baseline assessment with CMR, blood test, echocardiography, and 6-minute walk test and were followed up for mortality until the end of December 2013. Twelve patients (25%) died during follow-up, mostly from heart failure (50%). Impaired ventricular function (right or left ventricular ejection fraction) was associated with increased risk of mortality (lowest quartile: right ventricular ejection fraction, <40%; hazard ratio, 4.4 [95% confidence interval, 1.4-13.5]; P=0.01 and left ventricular ejection fraction, <50%; hazard ratio, 6.6 [95% confidence interval, 2.1-20.8]; P=0.001). Biventricular impairment (lowest quartile left ventricular ejection fraction, <50% and right ventricular ejection fraction, <40%) conveyed an even higher risk of mortality (hazard ratio, 8.0 [95% confidence interval, 2.5-25.1]; P=0.0004). No other CMR or noninvasive measurement besides resting oxygen saturation (hazard ratio, 0.90 [0.83-0.97]/%; P=0.007) was associated with mortality. CONCLUSIONS: Impaired right, left, or biventricular systolic function derived from baseline CMR and resting oxygen saturation are associated with mortality in adult patients with ES. CMR is a useful noninvasive tool, which may be incorporated in the risk stratification assessment of ES during lifelong follow-up.
Shao D, Garfied BE, Crosby A, et al., 2015, THE PROFILES OF JMJD3, UTX AND H3K27ME3 EXPRESSION IN PULMONARY VASCULATURE IN RAT MCT MODEL OF PAH AND HUMAN IPAH: IMPLICATIONS FOR PULMONARY ARTERIAL HYPERTENSION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ Publishing Group, Pages: A7-A8, ISSN: 0040-6376
Hewitt RJ, Dimopoulos K, Alexander D, et al., 2015, PERIOPERATIVE OUTCOMES IN PATIENTS WITH PULMONARY HYPERTENSION UNDERGOING NON-CARDIAC NON-OBSTETRIC SURGERY IN A DESIGNATED UK PULMONARY HYPERTENSION CENTRE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A214-A214, ISSN: 0040-6376
Garfield B, Shao D, Crosby A, et al., 2015, THE ROLE OF GROWTH AND DIFFERENTIATION FACTOR 15 IN SMOOTH MUSCLE CELL PROLIFERATION IN PULMONARY HYPERTENSION, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A213-A214, ISSN: 0040-6376
Ramakrishnan L, Mumby S, Wort S, et al., 2015, CD163 is expressed and modulated in human pulmonary artery smooth muscle cells: Implications for Pulmonary Artery Hypertension., ERS Annual Congress
Kempny A, Diller G-P, Dimopoulos K, et al., 2015, Determinants of outpatient clinic attendance amongst adults with congenital heart disease and outcome, International Journal of Cardiology, Vol: 203, Pages: 245-250, ISSN: 1874-1754
Background:Adult congenital heart disease (ACHD) guidelines advise life-long, regular, follow up in predefined intervals for ACHD patients. However, limited data exist to support this position. We examine, herewith, compliance to scheduled outpatient clinic appointments and its impact on outcome.Methods and results:We examined 4461 ACHD patients (median age at entry 26.4 years, 51% female) and their follow up records at our tertiary centre between 1991 and 2008. Clinic attendance was quantified from electronic hospital records. For survival analysis we employed the last clinic attendance before 2008 as starting of follow-up. Overall 23% of scheduled clinic appointments were not attended. The main predictors of clinic non-attendance (CNA) were younger age, non-Caucasian ethnicity, lower socioeconomic status, number of previous CNAs and the lack of planned additional investigation/s (e.g. echocardiography) scheduled on the same day. During a cumulative follow-up time of 48,828 patient-years, 366 (8.2%) patients died. Both, the number of CNAs (HR = 1.08, 95% CI 1.05–1.12 per CNA, P < 0.001) and the ratio of CNA to follow up period (HR = 1.23, 95% CI 1.04–1.44 per CNA/year, P = 0.013) emerged as predictors of mortality independent of adjustment for patients' age, disease complexity, functional class and socioeconomic status.Conclusions:Patient adherence to scheduled ACHD outpatient-clinics is associated with better survival. Identifying patients at an increased risk of CNA in a single tertiary centre is feasible. Our data provides previously lacking evidence supporting the practice of periodic assessment of ACHD patients at tertiary clinics. Non-attenders should be specifically targeted and receive counselling to modulate their increased risk of death.
Kumar N, Price LC, Montero MA, et al., 2015, Pulmonary tumour thrombotic microangiopathy: unclassifiable pulmonary hypertension?, EUROPEAN RESPIRATORY JOURNAL, Vol: 46, Pages: 1214-1217, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 30
Price LC, Shao D, Meng C, et al., 2015, Dexamethasone induces apoptosis in pulmonary arterial smooth musclecells, Respiratory Research, Vol: 16, ISSN: 1465-993X
BackgroundDexamethasone suppressed inflammation and haemodynamic changes inan animal model of pulmonary arterial hypertension (PAH). A majortarget for dexamethasone actions is NFκB, which is activated inpulmonary vascular cells and perivascular inflammatory cells in PAH.Reverse remodelling is an important concept in PAH disease therapy,and further to its antiproliferative effects, we sought to explore whetherdexamethasone augments pulmonary arterial smooth muscle cell(PASMC) apoptosis.MethodsAnalysis of apoptosis markers (caspase 3, insitu DNA fragmentation)and NFκB (p65 and phosphoIKKα/β) activation was performed onlung tissue from rats with monocrotaline (MCT)induced pulmonaryhypertension (PH), before and after day 14–28 treatment withdexamethasone (5 mg/kg/day). PASMC were cultured from this rat PHmodel and from normal human lung following lung cancer surgery.Following stimulation with TNFα (10 ng/ml), the effects ofdexamethasone (10 –10 M) and IKK2 (NFκB) inhibition12345−8 −6−626/08/2015 e.Proofinghttp://eproofing.springer.com/journals/printpage.php?token=z1f6oNo2TW2b02e3UtS87S7AQ0qS0Cpd07hxhERYg8 3/38(AS602868, 0–3 μM (03×10 M) on IL6 and CXCL8 release andapoptosis was determined by ELISA and by Hoechst staining. NFκBactivation was measured by TransAm assay.ResultsDexamethasone treatment of rats with MCTinduced PH in vivo led toPASMC apoptosis as displayed by increased caspase 3 expression andDNA fragmentation. A similar effect was seen in vitro using TNFαsimulated human and rat PASMC following both dexamethasone andIKK2 inhibition. Increased apoptosis was associated with a reduction inNFκB activation and in IL6 and CXCL8 release from PASMC.ConclusionsDexamethasone exerted reverseremodelling effects by augmentingapoptosis and reversing inflammation in PASMC possibly via i
Diller G-P, Kempny A, Alonso-Gonzalez R, et al., 2015, Survival prospects and circumstances of death in contemporary adult congenital heart disease patients under follow-up at a large tertiary centre, Circulation, Vol: 132, Pages: 2118-2125, ISSN: 0009-7322
Background—Adult congenital heart disease (ACHD) patients have ongoing morbidity and reduced long-term survival. Recently, the importance of specialized follow-up at tertiary ACHD centers has been highlighted. We aimed to assess survival prospects and clarify causes of death in a large cohort of patients at a single, tertiary center.Methods and Results—We included 6969 adult patients (age 29.9±15.4 years) under follow-up at our institution between 1991 and 2013. Causes of death were ascertained from official death certificates. Survival was compared with the expected survival in the general age- and sex-matched population, and standardized mortality rates were calculated. Over a median follow-up time of 9.1 years (interquartile range, 5.2–14.5), 524 patients died. Leading causes of death were chronic heart failure (42%), pneumonia (10%), sudden-cardiac death (7%), cancer (6%), and hemorrhage (5%), whereas perioperative mortality was comparatively low. Isolated simple defects exhibited mortality rates similar to those in the general population, whereas patients with Eisenmenger syndrome, complex congenital heart disease, and Fontan physiology had much poorer long-term survival (P<0.0001 for all). The probability of cardiac death decreased with increasing patient’s age, whereas the proportion of patients dying from noncardiac causes, such as cancer, increased.Conclusions—ACHD patients continue to be afflicted by increased mortality in comparision with the general population as they grow older. Highest mortality rates were observed among patients with complex ACHD, Fontan physiology, and Eisenmenger syndrome. Our data provide an overview over causes of mortality and especially the spectrum of noncardiac causes of death in contemporary ACHD patients.
Garfield B, Crosby A, Pieran Y, et al., 2015, The role of growth and differentiation factor 15 (GDF-15) in the development of skeletal muscle wasting in pulmonary arterial hypertension (PAH), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
- Author Web Link
- Cite
- Citations: 1
Garcia-Aranda B, Kempny A, Revilla-Martinez M, et al., 2015, Relation of the novel pulmonary hypertension emPHasis10 quality of life score to markers of disease severity, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Price L, Kempny A, Dimopoulos K, et al., 2015, Is sildenafil an effective bridging therapy to lung transplantation for patients with pulmonary hypertension in the setting of lung disease?, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Kempny A, Dimopoulos K, Alonso-Gonzalez R, et al., 2015, Multivariable mortality risk stratification in adult patients with eisenmenger syndrome, Congress of the European-Society-of-Cardiology (ESC), Publisher: Oxford University Press (OUP), Pages: 1138-1138, ISSN: 1522-9645
Kempny A, Diller GP, Alonso-Gonzalez R, et al., 2015, Survival Prospects and Circumstance of Death in Contemporary Adult Patients with Congenital Heart Disease: The Shifting Focus of Mortality from the Perioperative Period to Long-Term Complications, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1137-1137, ISSN: 0195-668X
Keir GJ, Nair A, Giannarou S, et al., 2015, Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection, Pulmonary Circulation, Vol: 5, Pages: 498-505, ISSN: 2045-8940
In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (−10%; range: −52.2% to 4.0%; P < 0.01), 20 minutes (−17.4%; −27.9% to 0.0%; P < 0.01), and 30 minutes (−8.5%; −34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold.
Dimopoulos K, Kempny A, Alonso-Gonzalez R, et al., 2015, Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension: Challenges and future directions, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 187, Pages: 401-403, ISSN: 0167-5273
- Author Web Link
- Cite
- Citations: 9
Chakrabarti AM, Mitchell JA, Wort SJ, 2015, Progress in the understanding and management of pulmonary arterial hypertension., Global Cardiology Science & Practice, Vol: 2015, ISSN: 2305-7823
Kempny A, Diller G-P, Alonso-Gonzalez R, et al., 2015, Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease, Heart, Vol: 101, Pages: 699-705, ISSN: 1355-6037
Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown.Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis.Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death.Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population.
Moceri P, Kempny A, Liodakis E, et al., 2015, Physiological differences between various types of Eisenmenger syndrome and relation to outcome, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 179, Pages: 455-460, ISSN: 0167-5273
- Author Web Link
- Cite
- Citations: 32
Shao D, Price L, Wort SJ, 2015, Molecular biological aspects, therapeutic targets and new treatment strategies, Treatment of Pulmonary Hypertension, Pages: 37-80, ISBN: 9783319135809
The term pulmonary arterial hypertension (PAH) describes a rare group of diseases characterized by raised pulmonary vascular resistance, resulting from vascular remodelling in the pre-capillary resistance arterioles (<100 �m in cross-sectional diameter) [1]. Left untreated, patients die from right heart failure, with a mortality approaching most serious cancers. To date, most treatment has been focused on the endothelial cell vascular dysfunction seen in these disorders. As such, pulmonary vasodilators, such as endothelin (ET-1) receptor antagonists, prostacyclin (PGI2) analogues and phosphodiesterase type V inhibitors (enhancing endogenous nitric oxide (NO)) have improved both morbidity and mortality. Indeed, there is continuing development into new and improved drugs that target these established pathways. Recent examples are the dual ET-1 receptor antagonist, macitentan [2], and the soluble guanylate cyclase activator, riociguat [3]. However, none are a cure and the treated mortality rate is still unacceptable [4]. Further research into the molecular mechanisms underpinning the pathogenesis of PAH has led to the discovery of new putative pathways that may allow the targeting of vascular remodelling itself; such "reverse remodelling" may provide a cure for this devastating disease in the future and remains the "holy grail".
Mumby S, Gambaryan N, Wort J, et al., 2015, Jq1, A Bromodomains And Extra-Terminal (bet) Protein Mimic, Decreases Remodelling And Inflammation In Pulmonary Vascular Cells: Implications For Pulmonary Arterial Hypertension, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Ramakrishnan L, Mumby S, Wort JS, et al., 2014, Ferroportin is Expressed in Human Pulmonary Artery Smooth Muscle Cells: Implications for Pulmonary Arterial Hypertension., BTS Annual Winter Meeting, Publisher: BMJ Publishing Group, ISSN: 1468-3296
Garfield BE, Parfitt L, Harries C, et al., 2014, QUALITY OF LIFE IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION IS ASSOCIATED WITH QUADRICEPS FUNCTION AND SIZE, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A76-A77, ISSN: 0040-6376
- Author Web Link
- Cite
- Citations: 1
Shao D, Wort SJ, 2014, THE ROLE OF SOLUBLE GUANYLATE CYCLASE STIMULATOR BAY 41-2272 ON REMODELLING PROCESSES RELEVANT TO THE PATHOGENESIS OF PULMONARY ARTERIAL HYPERTENSION, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A22-A23, ISSN: 0040-6376
Park JES, Lyon AR, Shao D, et al., 2014, Pulmonary venous hypertension and mechanical strain stimulate monocyte chemoattractant protein-1 release and structural remodelling of the lung in human and rodent chronic heart failure models, THORAX, Vol: 69, Pages: 1120-1127, ISSN: 0040-6376
- Author Web Link
- Cite
- Citations: 12
Mumby S, Gambaryan N, Adcock I, et al., 2014, THE BRD4 INHIBITOR, JQ1 DECREASES PROLIFERATION AND ARRESTS THE CELL CYCLE OF PULMONARY VASCULAR CELLS: IMPLICATIONS FOR PULMONARY ARTERIAL HYPERTENSION, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A22-A22, ISSN: 0040-6376
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.