Imperial College London

Professor Claire Shovlin

Faculty of MedicineNational Heart & Lung Institute

Professor of Practice (Clinical and Molecular Medicine)
 
 
 
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c.shovlin Website

 
 
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534 L BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

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83 results found

Shovlin CL, Buscarini E, Hughes JMB, Allison DJ, Jackson JEet al., Long terms outcomes of patients with pulmonary arteriovenous malformations considered for lung transplantation, compared to similarly hypoxemic cohorts, BMJ Open Respiratory Research, ISSN: 2052-4439

INTRODUCTION:Pulmonary arteriovenous malformations (PAVMs) may not be amenable to treatment by embolization or surgical resection, and many patients are left with significant hypoxemia. Lung transplantation has been undertaken.There is no guidance on selection criteria.METHODS:To guidetransplantation listingassessments, the outcomes of the six patients who had been considered for transplantation were compared to a similarly hypoxemic patient group recruited prospectively between2005-2016at thesame UK institution.RESULTS: Sixpatientshad been formally considered for lung transplantation purely for PAVMs. One underwent a single lung transplantation for diffuse PAVMs and died within 4 weeks of surgery. Theother five were not transplanted, in four cases at the patients’ request.Their current survival ranges from 16-27 (median 21) years post transplant assessment. Of 444 consecutive patients with PAVMs recruited between 2005-2016, 42 were similarly hypoxemic to the “transplant-considered”cohort (SaO2 <86.5%). Hypoxemic cohorts maintained arterial oxygen content through secondary erythrocytosis and higher haemoglobin. The “transplant-considered” cohort had similar CaO2to the hypoxemic comparator group,but higher MRC dyspnea scores(p=0.023),higher rates of cerebral abscesses (p=0.0043) and higher rates of venous thromboemboli (p=0.0009) that were evident before and after the decision to list for transplantation. CONCLUSIONS: The non-transplanted patients demonstrated marked longevity. Symptoms and co-morbidities were better predictors of health than oxygen measurements. While a case-by-case decision, weighing survival estimates and quality of life will help patients in their decision making, the data suggesta verystrong case must be made before lung transplantation is considered.

JOURNAL ARTICLE

Boother EJ, Brownlow S, Tighe HC, Bamford KB, Jackson JE, Shovlin CLet al., 2017, Cerebral abscess associated with odontogenic bacteremias, hypoxemia, and iron loading in immunocompetent patients with right-to-left shunting through pulmonary arteriovenous malformations., Clinical Infectious Diseases, Vol: 65, Pages: 595-603, ISSN: 1537-6591

Background: Cerebral abscess is a recognised complication of pulmonary arteriovenous malformations (PAVMs) that allow systemic venous blood to bypass the pulmonary capillary bed through anatomic right-to-left shunts. Broader implications and mechanisms remain poorly explored. Methods: Between June 2005 and December 2016, at a single institution, 445 consecutive adult patients with CT-scan confirmed PAVMs (including 403 (90.5%) with hereditary haemorrhagic telangiectasia) were recruited to a prospective series. Multivariate logistic regression, and detailed peri-abscess histories were evaluated to identify potential associations with cerebral abscess. Rates were compared to an earlier non-overlapping series. Results: Thirty-seven (8.3%) of the 445 patients experienced a cerebral abscesses at median age 50 (range 19-76) years. The rate adjusted for ascertainment bias was 27/435 (6.2%). 29/37 (78.4%) abscess patients had no PAVM diagnosis prior to their abscess, a rate unchanged from earlier UK series. 21/37 (56.7%) suffered residual neurological deficits, most commonly memory/cognition impairment; hemiparesis, and visual defects. Isolation of periodontal microbes, and precipitating dental and other interventional events emphasised potential sources of endovascular inoculations. In multivariate logistic regression, cerebral abscess was associated with low oxygen saturation (indicating greater right-to-left shunting); higher transferrin iron saturation index; intravenous iron use for anemia (adjusted odds ratio 5.4 [95% confidence intervals 1.4, 21.1]); male gender; and venous thromboemboli. There were no relationships with anatomic attributes of PAVMs, or red cell indices often increased due to secondary polycythemia. Conclusions: Greater appreciation of the risk of cerebral abscess in undiagnosed PAVMs is required. Lower SaO2 and intravenous iron may be modifiable risk factors.

JOURNAL ARTICLE

Finnamore H, Silva BM, Hickson BM, Whelan K, Shovlin CLet al., 2017, 7-day weighed food diaries suggest patients with hereditary hemorrhagic telangiectasia may spontaneously modify their diet to avoid nosebleed precipitants, ORPHANET JOURNAL OF RARE DISEASES, Vol: 12, ISSN: 1750-1172

JOURNAL ARTICLE

Hosman AE, Shovlin CL, 2017, Cancer and hereditary haemorrhagic telangiectasia, JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol: 143, Pages: 369-370, ISSN: 0171-5216

JOURNAL ARTICLE

Rizvi A, Macedo P, Babawale L, Tighe HC, Hughes JMB, Jackson JE, Shovlin CLet al., 2017, Hemoglobin Is a Vital Determinant of Arterial Oxygen Content in Hypoxemic Patients with Pulmonary Arteriovenous Malformations., Ann Am Thorac Soc, Vol: 14, Pages: 903-911

RATIONALE: PaO2 and SaO2 are commonly measured in respiratory practice, but arterial oxygen content (CaO2) refers to the volume of oxygen delivered to the tissues per unit blood volume. CaO2 is calculated from SaO2 and the hemoglobin concentration in blood, recognizing that each gram of hemoglobin can transport approximately 1.34 ml of oxygen when fully saturated. OBJECTIVES: To prospectively evaluate serial changes in CaO2 in humans, incorporating and excluding dynamic changes to oxygenation and hemoglobin parameters that may occur during life. METHODS: A cohort of 497 consecutive patients at risk of both hypoxemia and anemia were recruited. The patients had radiologically proven pulmonary arteriovenous malformations (PAVMs), which result in hypoxemia due to right-to-left shunting, and concurrent hereditary hemorrhagic telangiectasia, which placed them at risk of iron deficiency anemia due to recurrent hemorrhagic iron losses. Presentation SaO2 (breathing room air, by pulse oximetry), hemoglobin, red cell and iron indices were measured, and CaO2 calculated as SaO2 × hemoglobin × 1.34 ml/g. Serial measurements were evaluated in 100 cases spanning up to 32.1 (median, 10.5) years. RESULTS: Presentation CaO2 ranged from 7.6 to 27.5 (median, 17.6) ml/dl. CaO2 did not change appreciably across the SaO2 quartiles. In contrast, hemoglobin ranged from 5.9 to 21.8 g/dl (median, 14.1 g/dl), with a linear increase in CaO2 across hemoglobin quartiles. After PAVM embolization and an immediate increase in SaO2, hemoglobin fell and CaO2 was unchanged 1.6-12 (median, 4) months later. When hemoglobin fell because of iron deficiency, there was no change in SaO2. Similarly, when hemoglobin rose after iron treatment, there was no change in SaO2, and the expected CaO2 increment was observed. These relationships were not evident during pregnancy when hemoglobin fell, and PAVMs usually deteriorated: in pregnancy SaO2 commonly increased, and serial C

JOURNAL ARTICLE

Chamali B, Finnamore H, Manning R, Laffan MA, Hickson M, Whelan K, Shovlin CLet al., 2016, Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia - an observational study, INTRACTABLE & RARE DISEASES RESEARCH, Vol: 5, Pages: 109-113, ISSN: 2186-3644

JOURNAL ARTICLE

Mollet IG, Patel D, Govani FS, Giess A, Paschalaki K, Periyasamy M, Lidington EC, Mason JC, Jones MD, Game L, Ali S, Shovlin CLet al., 2016, Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes, PLOS ONE, Vol: 11, ISSN: 1932-6203

JOURNAL ARTICLE

Shovlin CL, Awan I, Cahilog Z, Abdulla FN, Guttmacher AEet al., 2016, Reported cardiac phenotypes in hereditary hemorrhagic telangiectasia emphasize burdens from arrhythmias, anemia and its treatments, but suggest reduced rates of myocardial infarction, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 215, Pages: 179-185, ISSN: 0167-5273

JOURNAL ARTICLE

Shovlin CL, Gilson C, Busbridge M, Patel D, Shi C, Dina R, Abdulla FN, Awan Iet al., 2016, Can Iron Treatments Aggravate Epistaxis in Some Patients With Hereditary Hemorrhagic Telangiectasia?, LARYNGOSCOPE, Vol: 126, Pages: 2468-2474, ISSN: 0023-852X

JOURNAL ARTICLE

Shovlin CL, Patel T, Jackson JE, 2016, Embolisation of PAVMs reported to improve nosebleeds by a subgroup of patients with hereditary haemorrhagic telangiectasia, ERJ Open Research, Vol: 2, ISSN: 2312-0541

JOURNAL ARTICLE

Gill SS, Roddie ME, Shovlin CL, Jackson JEet al., 2015, Pulmonary arteriovenous malformations and their mimics., Clin Radiol, Vol: 70, Pages: 96-110

Pulmonary arteriovenous malformations (PAVMs) are abnormal communications between the pulmonary arteries and veins, which result in a right-to-left (R-L) shunt with resultant hypoxemia, the severity of which will depend upon the size and number of lesions. Most PAVMs occur in individuals with hereditary haemorrhagic telangiectasia (HHT) and are a cause of serious morbidity and mortality largely related to cerebrovascular complications secondary to paradoxical embolization. The importance of their recognition and treatment by embolization, even in the absence of symptoms, is well known. Their appearances on chest radiographs are often, but not always, characteristic and the CT appearances are diagnostic; however, there are a number of both vascular and non-vascular diseases that can cause confusion. This review serves to highlight these PAVM "mimics".

JOURNAL ARTICLE

Shovlin CL, 2015, Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia, Frontiers in Genetics, Vol: 06, ISSN: 1664-8021

JOURNAL ARTICLE

Shovlin CL, Awan I, Abdulla FN, Govani FS, Mollet I, Patel Det al., 2015, One in twenty patients with hereditary hemorrhagic telangiectasia report iron treatments precipitate nosebleeds, Publisher: SPRINGER, Pages: 566-567, ISSN: 0969-6970

CONFERENCE PAPER

Yasuda W, Jackson JE, Layton DM, Shovlin CLet al., 2015, Hypoxaemia, sport and polycythaemia: a case from Imperial College London., Thorax, Vol: 70, Pages: 601-603, ISSN: 0040-6376

JOURNAL ARTICLE

Devlin HL, Hosman AE, Silva BM, Shovlin CLet al., 2014, Evaluation of anticoagulant and antiplatelet use in a haemorrhagic disorder, LANCET, Vol: 383, Pages: 40-40, ISSN: 0140-6736

JOURNAL ARTICLE

Elphick A, Shovlin CL, 2014, Relationships Between Epistaxis, Migraines, and Triggers in Hereditary Hemorrhagic Telangiectasia, LARYNGOSCOPE, Vol: 124, Pages: 1521-1528, ISSN: 0023-852X

JOURNAL ARTICLE

Finnamore HE, Whelan K, Hickson M, Shovlin CLet al., 2014, Top dietary iron sources in the UK, BRITISH JOURNAL OF GENERAL PRACTICE, Vol: 64, Pages: 172-173, ISSN: 0960-1643

JOURNAL ARTICLE

Howard LSGE, Santhirapala V, Murphy K, Mukherjee B, Busbridge M, Tighe HC, Jackson JE, Hughes JMB, Shovlin CLet al., 2014, Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations, CHEST, Vol: 146, Pages: 709-718, ISSN: 0012-3692

JOURNAL ARTICLE

Santhirapala V, Chamali B, McKernan H, Tighe HC, Williams LC, Springett JT, Bellenberg HR, Whitaker AJ, Shovlin CLet al., 2014, Orthodeoxia and postural orthostatic tachycardia in patients with pulmonary arteriovenous malformations: a prospective 8-year series, THORAX, Vol: 69, Pages: 1046-1047, ISSN: 0040-6376

JOURNAL ARTICLE

Shovlin CL, 2014, Pulmonary arteriovenous malformations., Am J Respir Crit Care Med, Vol: 190, Pages: 1217-1228

Within the past decade, pulmonary arteriovenous malformations (PAVMs) have evolved from rare curiosities to not uncommon clinical states, with the latest estimates suggesting a prevalence of ~1 in 2,600. PAVMs provide anatomic right-to-left shunts, allowing systemic venous blood to bypass gas exchange and pulmonary capillary bed processing. Hypoxemia and enhanced ventilatory demands result, although both are usually asymptomatic. Paradoxical emboli lead to strokes and cerebral abscesses, and these commonly occur in individuals with previously undiagnosed PAVMs. PAVM hemorrhage is rare but is the main cause of maternal death in pregnancy. PAVM occlusion by embolization is the standard of care to reduce these risks. However, recent data demonstrate that currently recommended management protocols can result in levels of radiation exposure that would be classified as harmful. Recent publications also provide a better appreciation of the hematologic and cardiovascular demands required to maintain arterial oxygen content and oxygen consumption in hypoxemic patients, identify patient subgroups at higher risk of complications, and emphasize the proportion of radiologically visible PAVMs too small to treat by embolization. This review, therefore, outlines medical states that exacerbate the consequences of PAVMs. Chief among these is iron deficiency, which is commonly present due to concurrent hereditary hemorrhagic telangiectasia: iron deficiency impairs hypoxemia compensations by restricting erythropoiesis and increases the risk of ischemic strokes. Management of periodontal disease, dental interventions, pulmonary hypertension, and pregnancy also requires specific consideration in the setting of PAVMs. The review concludes by discussing to what extent previously recommended protocols may benefit from modification or revision.

JOURNAL ARTICLE

Shovlin CL, 2014, Iron deficiency, ischaemic strokes, and right-to-left shunts: From pulmonary arteriovenous malformations to patent foramen ovale?, Intractable Rare Dis Res, Vol: 3, Pages: 60-64, ISSN: 2186-3644

Has the recent identification of iron deficiency as a risk factor for ischaemic stroke in patients with pulmonary arteriovenous malformations (AVMs) unmasked a new paradigm for stroke/infarct pathogenesis? This commentary reviews evidence that spans associations between iron deficiency and ischaemic strokes, iron deficiency enhancement of platelet aggregation in response to serotonin/5HT, settings in which plasma 5HT is elevated, and clinical trial confirmation that 5HT receptor antagonists prevent ischaemic stroke. The critical leap which directs attention away from atherothrombotic events at the neurovascular wall is that ischaemic strokes due to pulmonary AVMs are attributable to compromised pulmonary capillary bed filtration of venous blood. Right-to-left shunting is continuous through pulmonary AVMs, but also occurs intermittently in approximately 30% of the general population with intracardiac shunts such as patent foramen ovale (PFO). The testable hypothesis presented is that paradoxical embolism of venous platelet-based aggregates may constitute part of the causal chain between iron deficiency and ischaemic stroke, not only in the rare disease state of pulmonary AVMs, but also in major subgroups of the general population.

JOURNAL ARTICLE

Shovlin CL, 2014, Curable hypoxia in an octogenarian with an undiagnosed inherited condition: a case commentary, Breathe, Vol: 10, Pages: 153-156

JOURNAL ARTICLE

Shovlin CL, Chamali B, Santhirapala V, Livesey JA, Angus G, Manning R, Laffan MA, Meek J, Tighe HC, Jackson JEet al., 2014, Ischaemic Strokes in Patients with Pulmonary Arteriovenous Malformations and Hereditary Hemorrhagic Telangiectasia: Associations with Iron Deficiency and Platelets, PLOS ONE, Vol: 9, ISSN: 1932-6203

JOURNAL ARTICLE

Shovlin CL, Ganesan V, 2014, Hereditary hemorrhagic telangiectasia, Up to Date in Clinical Medicine, Editors: Ternauer

BOOK CHAPTER

Devlin HL, Hosman AE, Shovlin CL, 2013, Antiplatelet and Anticoagulant Agents in Hereditary Hemorrhagic Telangiectasia, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 368, Pages: 876-878, ISSN: 0028-4793

JOURNAL ARTICLE

Finnamore H, Le Couteur J, Hickson M, Busbridge M, Whelan K, Shovlin CLet al., 2013, Hemorrhage-Adjusted Iron Requirements, Hematinics and Hepcidin Define Hereditary Hemorrhagic Telangiectasia as a Model of Hemorrhagic Iron Deficiency, PLOS ONE, Vol: 8, ISSN: 1932-6203

JOURNAL ARTICLE

Govani FS, Giess A, Mollet IG, Begbie ME, Jones MD, Game L, Shovlin CLet al., 2013, Directional next-generation RNA sequencing and examination of premature termination codon mutations in endoglin/hereditary haemorrhagic telangiectasia., Mol Syndromol, Vol: 4, Pages: 184-196, ISSN: 1661-8769

Hereditary haemorrhagic telangiectasia (HHT) is a disease characterised by abnormal vascular structures, and most commonly caused by mutations in ENG, ACVRL1 or SMAD4 encoding endothelial cell-expressed proteins involved in TGF-β superfamily signalling. The majority of mutations reported on the HHT mutation database are predicted to lead to stop codons, either due to frameshifts or direct nonsense substitutions. The proportion is higher for ENG (67%) and SMAD4 (65%) than for ACVRL1 (42%), p < 0.0001. Here, by focussing on ENG, we report why conventional views of these mutations may need to be revised. Of the 111 stop codon-generating ENG mutations, on ExPASy translation, all except one were premature termination codons (PTCs), sited at least 50-55 bp upstream of the final exon-exon boundary of the main endoglin isoform, L-endoglin. This strongly suggests that the mutated RNA species will undergo nonsense-mediated decay. We provide new in vitro expression data to support dominant negative activity of stable truncated endoglin proteins but suggest these will not generate HHT: the single natural stop codon mutation in L-endoglin (sited within 50-55 nucleotides of the final exon-exon boundary) is unlikely to generate functional protein since it replaces the entire transmembrane domain, as would 8 further natural stop codon mutations, if the minor S-endoglin isoform were implicated in HHT pathogenesis. Finally, next-generation RNA sequencing data of 7 different RNA libraries from primary human endothelial cells demonstrate that multiple intronic regions of ENG are transcribed. The potential consequences of heterozygous deletions or duplications of such regions are discussed. These data support the haploinsufficiency model for HHT pathogenesis, explain why final exon mutations have not been detected to date in HHT, emphasise the potential need for functional examination of non-PTC-generating mutations, and lead to proposals for an alternate stratification system o

JOURNAL ARTICLE

Hosman AE, Devlin HL, Silva BM, Shovlin CLet al., 2013, Specific cancer rates may differ in patients with hereditary haemorrhagic telangiectasia compared to controls, ORPHANET JOURNAL OF RARE DISEASES, Vol: 8, ISSN: 1750-1172

JOURNAL ARTICLE

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