Clinical Outcomes of Pulmonary Arterial Hypertension in Patients Carrying an <i>ACVRL1</i> (<i>ALK1</i>) Mutation

Girerd, Barbara; Montani, David; Coulet, Florence; Sztrymf, Benjamin; Yaïci, Azzedine; Jaïs, Xavier; Trégouët, David‐Alexandre; Reis, Abílio; Drouin‐Garraud, Valérie; Fraisse, Alain; Sitbon, Olivier; O’Callaghan, Dermot S.; Simonneau, Gérald; Soubrier, Florent; Humbert, Marc

doi:10.1164/rccm.200908-1284oc

Cited by 263 publications

(247 citation statements)

References 46 publications

(88 reference statements)

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“…3,6,7 The majority of PAVM patients have underlying hereditary hemorrhagic telangiectasia(HHT), 11,17,18 but overall, pulmonary hypertension is uncommon in PAVM/HHT patients. 12 When pulmonary hypertension does occur, 19,20 this results not from hypoxia, but from other pathophysiological processes, particularly pulmonary arterial hypertension, 12,[21][22][23][24] and pulmonary venous hypertension associated with hepatic AVMs and high outputs states. 12,[25][26][27] Our hypothesis was that in the presence of hypoxemia but absence of pulmonary hypertension, exercise capacity can be maintained by cardiovascular andhematological 28 adaptations.…”

Section: ṽO2mentioning

confidence: 99%

Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations

Howard

Santhirapala

Murphy

et al. 2014

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Section: ṽO2mentioning

confidence: 99%

Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations

Howard

Santhirapala

Murphy

et al. 2014

Chest

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“…While pulmonary arterial hypertension does affect a subgroup of HHT patients, the real risk is probably closer to 1-2%, 16,101 and is genotype-dependant. 102 Thirdly, the majority of affected individuals still remain undiagnosed: In 121 (59%) of 205 consecutive individuals with pulmonary AVMs and HHT reviewed at one UK institution, the diagnosis of HHT had not been made previously. 34 Careful and unbiassed epidemiological studies are required to unmask all HHT-affected individuals, especially those with potentially lesser symptoms than in hospital-based series.…”

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confidence: 99%

“…Juvenile polyposis (JP) occurs in patients with SMAD4 mutations, when it appears to be indistinguishable from JP caused by BMPRIA mutations. In man (but not in mouse 133 ), pulmonary arterial hypertension occurs predominantly and possibly exclusively within HHT2 patients 102,134,135 , when it may have a worse prognosis than when due to BMPR2 mutations 102 . HHT2 patients are also at higher risk of post capillary pulmonary hypertension associated with hepatic AVMs.…”

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confidence: 99%

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

2010

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Hereditary haemorrhagic telangiectasia, inherited as an autosomal dominant trait, affects approximately 1 in 5,000 people. The abnormal vascular structures in HHT result from mutations in genes (most commonly endoglin or ACVRL1) whose protein products influence TGF-ß superfamily signalling in vascular endothelial cells. The cellular mechanisms underlying the generation of HHT telangiectasia and arteriovenous malformations are being unravelled, with recent data focussing on a defective response to angiogenic stimuli in particular settings. For affected individuals, there is often substantial morbidity due to sustained and repeated haemorrhages from telangiectasia in the nose and gut. Particular haematological clinical challenges include the management of severe iron deficiency anaemia; handling the intricate balance of antiplatelet or anticoagulants for HHT patients in whom there are often compelling clinical reasons to use such agents; and evaluation of apparently attractive experimental therapies promoted in high profile publications when guidelines and reviews are quickly superseded. There is also a need for sound screening programmes for silent arteriovenous malformations. These occur commonly in the pulmonary, cerebral, and hepatic circulations, may haemorrhage, but predominantly result in more complex pathophysiology due to consequences of defective endothelium, or shunts that bypass specific capillary beds. This review will focus on the new evidence and concepts in this complex and fascinating condition, placing these in context for both clinicians and scientists, with a particular emphasis on haematological settings. Blood Reviews _ HHT 2010_ Shovlin 3 Overview of HHTHHT, also known as Osler Weber Rendu syndrome [1][2][3] , is one of the most common disorders to be inherited as an autosomal dominant trait. Careful epidemiological studies reveal that it affects approximately 1 in 5,000 individuals, 4,5 with regional differences, 6 and isolated communities displaying higher prevalences due to founder effects. 7 8 HHT was first described as a familial disease characterised by severe recurrent nasal and gastrointestinal bleeding with associated anaemia, and visible dilated blood vessels (telangiectasia) on the lips and finger tips. The majority of HHT patients are also affected by larger arteriovenous malformations (AVMs) in the pulmonary, hepatic, cerebral, pancreatic, spinal and other circulations. 1,2,9 These features, presented in more detail within Table 1, are used as criteria to diagnose HHT. 2 The spectrum of disease within the HHT umbrella has extended beyond the telangiectatic/AVM HHT pathology delineated by the Curaçao criteria. 2 More recently recognised features include pulmonary arterial hypertension 10 ; juvenile polyposis 11 ; pulmonary hypertension in the context of high output cardiac failure secondary to hepatic AVMs, when PH may be reversible after hepatic AVM treatment [12][13][14][15][16] ; a prothrombotic state associated with elevated plasma levels of factor VIII 17 , and poten...

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“…Histological proof of veno-occlusive disease was based on haematoxylineosin-safran staining of biopsies (n51), post mortem (n51) or lungs obtained after lung transplantation (n510). The pathological hallmark of PVOD was defined as an extensive and diffuse obstruction of pulmonary veins and venules by intimal fibrosis, cellular proliferation and muscularisation [10,[18][19][20]. As a control group, we reviewed 70 consecutive V9/Q9 lung scans performed at time of diagnosis in patients with idiopathic or heritable PAH (PAH group) diagnosed between 2007 and 2009.…”

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confidence: 99%

Ventilation/perfusion lung scan in pulmonary veno-occlusive disease

et al. 2011

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Pulmonary veno-occlusive disease (PVOD), a rare form of pulmonary arterial hypertension (PAH), requires histological proof for definitive diagnosis; however, lung biopsy is not recommended in PAH. Recent conjoint European Respiratory Society/European Society of Cardiology guidelines suggest that nonmatched perfusion defects on ventilation/perfusion (V9/Q9) lung scanning in PAH patients may suggest PVOD. The aim of our study was to evaluate V9/Q9 lung scans in a large cohort of PVOD and idiopathic or heritable PAH patients.V9/Q9 lung scans from 70 patients with idiopathic or heritable PAH and 56 patients with confirmed or highly probable PVOD were reviewed in a double-blind manner.The vast majority of V9/Q9 lung scans were normal or without significant abnormalities in both groups. No differences in ventilation or perfusion lung scans were observed between PAH and PVOD patients (all p.0.05). Furthermore, no differences were observed between confirmed (n531) or highly probable PVOD (n525). Nonmatched perfusion defects were found in seven (10%) idiopathic PAH patients and four (7.1%) PVOD patients (p.0.05).Nonmatched perfusion defects were rarely seen in a large cohort of idiopathic or heritable PAH and PVOD patients. Future recommendations should be amended according to these results suggesting that V9/Q9 lung scanning is not useful in discriminating PVOD from idiopathic PAH.

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Clinical Outcomes of Pulmonary Arterial Hypertension in Patients Carrying an ACVRL1 (ALK1) Mutation

Abstract: ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis. Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression.

Cited by 263 publications

References 46 publications

Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations

Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations

Hereditary haemorrhagic telangiectasia: Pathophysiology, diagnosis and treatment

Ventilation/perfusion lung scan in pulmonary veno-occlusive disease

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