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Treat-to-target approach in pulmonary arterial hypertension: a consensus-based proposal #34

The study of risk in pulmonary arterial hypertension. #35

Exercise testing in the clinical management of patients affected by pulmonary arterial hypertension. #6

Predicting survival in pulmonary arterial hypertension in the UK.  #12

- And 38 other recent publications
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1. Circ J. 2013 Feb 5. [Epub ahead of print]

Optical Coherence Tomography Is Superior to Intravascular Ultrasound for Diagnosis of Distal-Type Chronic Thromboembolic Pulmonary Hypertension.

Tatebe SFukumoto YSugimura KMiura YNochioka KAoki TMiura MYamamoto SYaoita NSatoh K,Shimokawa H.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine.
Free Article
  PMID: 23386271 [PubMed - as supplied by publisher]
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2. BMJ Case Rep. 2013 Feb 1;2013. pii: bcr2012008352. doi: 10.1136/bcr-2012-008352.

Pulmonary hypertension in a patient with hereditary haemorrhagic telangiectasia.

Chadha DHanda AKumar A.
Department of Cardiology, MH (CTC), Pune, Maharashtra, India.


A young male patient reported for evaluation of progressive easy fatigability, accompanied by a recent history of recurrent haemoptysis. His clinical examination was unremarkable except for evidence of pulmonary arterial hypertension (PAH). Routine investigations (haemogram, coagulogram, serological tests for connective tissue disorders and a sputum Ziehl Neelsen stain for acid-fast bacilli) were normal. Two-dimensional echocardiography suggested PAH (pulmonary artery systolic pressure-67 mm Hg), whereas the 64-slice spiral CT pulmonary angiogram showed a dilated main pulmonary artery along with bilateral arteriovenous malformations. Cardiac catheterisation performed subsequently confirmed the presence of PAH. On the basis of the above findings, a diagnosis of hereditary haemorrhagic telangiectasia (HHT) complicated with PAH was made, and the patient was started on oral sildenafil therapy to which he responded well. This rare complication of HHT, which requires a high degree of suspicion for diagnosis, is discussed.
  PMID: 23378554 [PubMed - in process]
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3. BMJ Case Rep. 2013 Feb 1;2013. pii: bcr2012007752. doi: 10.1136/bcr-2012-007752.

Pulmonary veno-occlusive disease: an uncommon cause of pulmonary hypertension.

Masters KBennett S.
Department of Medicine, Madigan Army Medical Center, Tacoma, Washington, USA.


Pulmonary veno-occlusive disease (PVOD) is a rare and challenging cause of pulmonary hypertension. Clinical presentation is non-specific, including dyspnoea, cough and fatigue. Diagnosis of PVOD is typically based on high clinical suspicion with a definitive diagnosis confirmed by histology. Our case involves a healthy 21-year-old man who developed dyspnoea on exertion at an elevated altitude during deployment to Afghanistan. His work-up included an echocardiogram, a high-resolution CT scan, V/Q scan, pulmonary function tests with diffusion capacity, and a cardiac catheterisation with vasodilator challenge. Initially diagnosed with vasodilator responsive pulmonary arterial hypertension, an oral vasodilator was given with subsequent development of non-cardiogenic pulmonary oedema, thus confirming a clinical diagnosis of PVOD. He was medically stabilised with diuretic therapy, but developed progressive right-ventricular failure. For definitive treatment, he underwent a successful bilateral lung transplant. Explanted lung histology confirmed the diagnosis of PVOD.
  PMID: 23378546 [PubMed - in process]
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4. Am J Respir Cell Mol Biol. 2013 Feb;48(2):iii-v. doi: 10.1165/rcmb.2012-0441ED.

Beyond pulmonary hypertension: sildenafil for chronic lung disease of prematurity.

Steinhorn RHKinsella JPAbman SH.
  PMID: 23378489 [PubMed - in process]
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5. Pulm Circ. 2012 Oct;2(4):407-14. doi: 10.4103/2045-8932.105029.

Cross talk between autophagy and apoptosis in pulmonary hypertension.

Jin YChoi AM.
Division of Pulmonary and Critical Care, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.


Endothelial cell (EC) apoptosis and apoptosis resistant proliferation have been proposed to play crucial roles in the development of featured plexiform lesions in the pathogenesis of pulmonary hypertension (PH). Subsequently, EC injury associated smooth muscle cell (SMC) proliferation facilitates vascular remodeling and eventually leads to narrowed vascular lumen, increased pulmonary vascular resistance, increased pulmonary arterial pressure, and right heart failure. The imbalance between cell death and proliferation occurs in every stage of pulmonary vascular remodeling and pathogenesis of PH, and involves every cell type in the vasculature including, but not limited to ECs, SMCs, and fibroblasts. Despite extensive studies, the detailed cellular and molecular mechanisms on how the transition from initial apoptosis of ECs to apoptosis resistant proliferation on ECs and SMCs remains unclear. Recent knowledge on autophagy, a conservative and powerful regulatory machinery existing in almost all mammalian cells, has shed light on the complex and delicate control on cell fate in the development of vascular remodeling in PH. In this review, we will discuss the recent understandings on how the cross-talk between apoptosis and autophagy regulates cell death or proliferation in PH pathogenesis, particularly in pulmonary vascular remodeling involving ECs and SMCs.
PMCID: PMC3555411 Free PMC Article
  PMID: 23372925 [PubMed]
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6. Eur J Prev Cardiol. 2012 Oct;19(5):960-71.

Exercise testing in the clinical management of patients affected by pulmonary arterial hypertension.

Paolillo SFarina SBussotti MIorio APerroneFilardi PPiepolil MFAgostoni P.
Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples, Italy.


Patients affected by pulmonary arterial hypertension (PAH) show a reduced exercise tolerance with early occurrence of dyspnoea and fatigue. The origin of functional capacity limitation is multifactorial and several mechanisms have been proposed, including right heart failure, which leads to a limited increase in cardiac output during exercise, and hyperventilation with a reduced perfusion of properly ventilated alveoli. In addition, abnormalities in arterial blood gases are observed, with the occurrence of hypoxemia and hypocapnia, related to an abnormal ventilation/perfusion match, gas diffusion abnormalities, low mixed venous oxygen saturation and to the development of intra- and extra-pulmonary right-to-left shunts. At present, the 6-minute walking test is the most used method to assess exercise tolerance in PAH; it is also useful to monitor the response to therapy and provides prognostic information. However, the assessment of functional capacity by cardiopulmonary exercise test (CPET) seems to be more complete, because CPET allows for discrimination between the metabolic, cardiovascular and pulmonary components of exercise limitation. Moreover, CPET estimates the severity of disease and assesses patients' prognosis and response to therapy. In PAH, a typical CPET-response is observed, characterized by a severe reduction in peak VO2, work rate, O2 pulse and anaerobic threshold and by a marked increase in VE/VCO2 slope and in the dead space to tidal volume ratio. However, the use of CPET should be limited to experienced centres. This review will focus on resting lung function and exercise tolerance tests, showing that CPET can provide the physiological explanation of functional limitation in PAH.
  PMID: 23126000 [PubMed - indexed for MEDLINE]
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7. Circ J. 2012;76(9):2249-54. Epub 2012 Jun 13.

Maternal outcome in pregnancy complicated with pulmonary arterial hypertension.

Katsuragi SYamanaka KNeki RKamiya CSasaki YOsato KMiyoshi TKawasaki KHoriuchi CKobayashi YUeda KYoshimatsu JNiwa KTakagi YOgo TNakanishi NIkeda T.
Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, Suita,



Pulmonary arterial hypertension (PAH), including Eisenmenger syndrome, has a risk of mortality in pregnancy of 10-40%. The aim of this study was to investigate whether pulmonary artery blood pressure (PABP) is a prognostic factor for pregnancy outcome in patients with PAH.


The subjects were 42 patients with PAH during pregnancy. Severe and mild cases were defined by PABP before and during the first 14 weeks of pregnancy, with severe cases having mean PABP >40 mmHg by catheterization or systolic PABP >50 mmHg on echocardiography. Eighteen women chose termination of pregnancy before 14 weeks, leaving 24 women (10 mild, 14 severe) for analysis. The women with severe PAH delivered earlier (35.4 vs. 31.5 weeks, P<0.05) and had higher rates of small-for-gestational-age infants (0/10 vs. 7/14, P<0.01). Among the women with severe PAH, the New York Heart Association class dropped by 1 in 9 cases, by 2 in 3 cases, and remained the same in 2 cases as pregnancy progressed, whereas among the women with mild PAH, the class dropped by 1 in 1 case and 9 women remained in the same class. Among the severe cases, 1 woman died and there was 1 fetal death; PABP markedly increased in later pregnancy from 54 to 74 mmHg (catheter measurement) and from 78 to 93 mmHg (echocardiography) (P<0.05).


The level of PABP before or in the early stage of pregnancy is an important predictor of pregnancy outcome.  
Free Article
  PMID: 22785004 [PubMed - indexed for MEDLINE]
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8. Chest. 2013 Jan 31. doi: 10.1378/chest.12-2296. [Epub ahead of print]

Iloprost Improves Gas Exchange in Patients with Pulmonary Hypertension and ARDS.

Sawheny EEllis ALKinasewitz GT.



We hypothesized that nebulized iloprost would improve ventilation perfusion matching in patients with pulmonary hypertension and acute respiratory distress syndrome (ARDS) as reflected by an improved PaO2/FIO2 ratio and PaO2 without adversely affecting lung mechanics or systemic hemodynamics.


ARDS patients with pulmonary hypertension were enrolled. With constant ventilator settings, hemodynamics, airway pressures and gas exchange measured at baseline were compared to values 30 min after 10 mcg nebulized Iloprost, and again 30 min after a second dose of 20 mcg of iloprost and finally 2 h after the second dose. The primary outcome variable was PaO2 while secondary outcomes were PaO2/FIO2 ratio, mean arterial BP, and lung compliance ventilatory equivalents for O2 and CO2.


After informed consent was obtained 20 patients (9 male and 11 female, median age 59 ((IQR 44 to 66)) years, with ARDS were enrolled. Baseline PaO2 improved from 82(±13) mmHg to 100(±25) and 100(±25) mmHg after the 1st and 2nd doses of iloprost respectively, while, PaO2/FIO2 ratio of 177(±60) improved to 213(±67) and 212(±70) (all p&lt;0.01). PaCO2, peak and plateau airway pressures, systemic blood pressure and heart rate were not significantly changed after iloprost.


The improvement in gas exchange without any detrimental effects on pulmonary mechanics or systemic hemodynamics suggests nebulized iloprost may be a useful therapeutic agent to improve oxygenation in patients with ARDS.ClinTrials.govNCT01274481.
  PMID: 23370599 [PubMed - as supplied by publisher]
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9. Eur Respir J. 2012 Sep;40(3):533-4. doi: 10.1183/09031936.00095612.

The key or just a cog in the wheel to operability assessment?

Kim NH.
  PMID: 22941544 [PubMed - indexed for MEDLINE]
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10. Eur Respir J. 2012 Sep;40(3):530-2. doi: 10.1183/09031936.00094112.

Survivor bias and risk assessment.

Miller DPGomberg-Maitland MHumbert M.
  PMID: 22941543 [PubMed - indexed for MEDLINE]
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11. Eur Respir J. 2012 Sep;40(3):750-65. doi: 10.1183/09031936.00025212. Epub 2012 Jul 12.

Imaging of sarcoidosis of the airways and lung parenchyma and correlation with lung function.

Nunes HUzunhan YGille TLamberto CValeyre DBrillet PY.
Department of Pneumology, University of Paris 13, UPRES EA 2363, Assistance Publique-Hôpitaux de Paris, Avicenne Hospital, Bobigny, France.


Imaging has a prominent role in the assessment of sarcoidosis diagnosis and outcome, which are extremely variable. Chest radiography staging helps predict the probability of spontaneous remission, and stage IV is associated with higher mortality. However, the reproducibility of reading is poor and changes in radiography and lung function are inconsistently correlated, which may be problematic for the monitoring of disease and treatment response. Chest computed tomography (CT) makes a great diagnostic contribution in difficult cases. Bilateral hilar lymphadenopathy with peri-lymphatic micronodular pattern is highly specific for sarcoidosis. CT is important for the investigation of pulmonary complications, including aspergilloma and pulmonary hypertension. CT improves the yield of bronchoscopy for obtaining a positive endobronchial or transbronchial biopsy. CT findings may also discriminate between active inflammation and irreversible fibrosis, with occasional influence on therapeutic decisions. Three CT patterns of fibrotic sarcoidosis are identified, with different functional profiles: predominant bronchial distortion is associated with obstruction; honeycombing is associated with restriction and lower diffusing capacity of the lung for carbon monoxide; whereas functional impairment is relatively minor with linear pattern. The clinical impact of correlations between CT severity scores and functional impairment is uncertain, except for its utility elucidating the mechanisms of airflow limitation, which include bronchial distortion, peribronchovascular thickening, air-trapping and bronchial compression by lymphadenopathy.
  PMID: 22790910 [PubMed - indexed for MEDLINE]
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12. Eur Respir J. 2012 Sep;40(3):604-11. doi: 10.1183/09031936.00196611. Epub 2012 May 3.

Predicting survival in pulmonary arterial hypertension in the UK.

Lee WTLing YSheares KKPepke-Zaba JPeacock AJJohnson MK.
Scottish Pulmonary Vascular Unit, Level 1, Golden Jubilee National Hospital, Agamemnon Street, Clydebank, Glasgow, G81 4DY, UK.


Contemporary prognostic equations in pulmonary arterial hypertension (PAH) derived from US and French cohorts may not perform as well in the UK as a locally derived scoring scheme. The aim of the study was to develop and validate a UK risk score to predict prognosis in PAH. Baseline mortality predictors identified by multivariate Cox analysis in 182 incident PAH patients were used to derive the Scottish composite score (SCS). Its prognostic performance in an independent UK cohort was compared with the French registry and Pulmonary Hypertension Connection (PHC) registry equations using Brier scores (BS). The SCS based on age, sex, aetiology, right atrial pressure, cardiac output and 6-min walk distance predicted survival in the validation cohort (hazard ratio (HR) 1.7 per point increase; p<0.001) and provided further prognostic stratification in World Health Organization (WHO) functional class III patients (HR 1.8 per point increase; p<0.001). It was more accurate than the French registry equation in predicting 1-yr survival (BS: 0.092 versus 0.146; p=0.001) and 2-yr survival (0.131 versus 0.255; p<0.001). There was no significant difference in BS between the SCS and PHC registry equation. The SCS predicts survival and can be used to supplement WHO functional class in prognostication.
  PMID: 22556026 [PubMed - indexed for MEDLINE]
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13. Rheumatology (Oxford). 2013 Feb 12. [Epub ahead of print]

Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature.

Gunnarsson RAndreassen AKMolberg OLexberg ASTime KDhainaut ASBertelsen LTPalm OIrgens KBecker-Merok ANordeide JLJohnsen VPedersen SPrøven AGarabet LSGaren TAaløkken TMGilboe IMGran JT.
Rheumatology Unit, Oslo University Hospital Rikshospitalet, Institute of Clinical Medicine, University of Oslo, Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Department of Rheumatology, Buskerud Hospital, Drammen, Haugesund Rheumatism Hospital, Haugesund, Department of Rheumatology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Department of Rheumatology, Haukeland University Hospital, Bergen, Department of Rheumatology, Ålesund Hospital, Ålesund, Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Department of Rheumatology, Førde Central Hospital, Førde, Department of Rheumatology, Sørlandet Hospital, Kristiansand, Department of Rheumatology, Nordland Hospital, Bodø, Department of Rheumatology, Martina Hansens Hospital, Bærum, Department of Rheumatology, Østfold Hospital, Moss, Norwegian Systemic Tissue Disease and Vasculitides Registry, Oslo University Hospital, Oslo and Department of Radiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.


Objectives. The aim of this study was to assess the overall prevalence of pulmonary hypertension (PH) in an unselected MCTD cohort and review the current knowledge with a systematic database search.Methods. A nationwide multicentre cohort of 147 adult MCTD patients were initially screened for PH by echocardiography, high-resolution computed tomography (HRCT), pulmonary function tests and N-terminal pro-brain natriuretic peptide (NT-proBNP) and then followed up for a mean of 5.6 years. Right-sided heart catheterization was performed when estimated pulmonary artery systolic pressure was >40 mmHg on echocardiography. PH was diagnosed according to the 2009 European Society of Cardiology and European Respiratory Society guidelines.Results. At inclusion, 2.0% (3/147) had established PH. Two additional PH patients were identified during follow-up, giving a total PH frequency in the cohort of 3.4% (5/147). All five had elevated serum NT-proBNP. Two had isolated pulmonary arterial hypertension (PAH) and three PH associated with interstitial lung disease (PH-ILD). Three PH patients died during follow-up. Nine other patients in the cohort also died, but none of them had echocardiographic signs of PH prior to death.Conclusion. The data from the current unselected MCTD cohort suggest that the prevalence of PH is much lower than expected from previous studies but confirm the seriousness of the disease complication.
  PMID: 23407386 [PubMed - as supplied by publisher]
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14. Int J Tuberc Lung Dis. 2013 Mar;17(3):406-11. doi: 10.5588/ijtld.12.0428.

Sarcoidosis-associated pulmonary hypertension in patients with near-normal lung function.

Maimon NSalz LShershevsky YMatveychuk AGuber AShitrit D.
Pulmonary Institute, Soroka University Medical Center, Beer Sheva, Israel.



Tertiary care medical centre in Israel.


Pulmonary hypertension (PH) is a predictor of poor outcome in patients with sarcoidosis. Early diagnosis may improve outcome.


To determine factors that might contribute to the early diagnosis of PH in sarcoidosis patients with near normal lung function tests.


Retrospective patient review.


Data from 127 patients with sarcoidosis and near normal lung function tests (forced vital capacity > 70%, forced expiratory volume in 1 second > 70% and diffusion capacity of carbon monoxide [D(LCO)] > 60%), who underwent high resolution computed tomography (HRCT) scan, the 6-minute walk distance (6MWD) test and echocardiogram were analysed. Demographic, clinical and HRCT findings were compared between patients with and those without PH.


Thirty-six patients (28.3%) had PH. Patients with PH tended to have lower D(LCO) (68% ± 8 vs. 75% ± 17, P = 0.038), 6MWD (308 m ± 106 vs. 486 m ± 99, P = 0.009) and exercise saturation (91 ± 4 vs. 95 ± 3, P = 0.0001) compared to those without PH. HRCT patterns in PH showed higher frequencies of interstitial thickening (P = 0.004), ground glass appearance (P = 0.01) and fibrosis (P = 0.032). In logistic regression, only 6MWD was predictive of PH (P = 0.005, 95%CI 0.970-0.995).


Physiological and radiographic characteristics appeared to differentiate patients with PH from those without. Physicians should be aware of PH in patients with sarcoidosis, even in those with near normal lung function.
  PMID: 23407231 [PubMed - in process]
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15. Ren Fail. 2013 Feb 14. [Epub ahead of print]

Pulmonary Hypertension in Dialysis Patients.

Kosmadakis GAguilera DCarceles ODa Costa Correia EBoletis I.
Nephrology Unit, Laiko General Hospital , Athens , Greece.


Pulmonary hypertension in end-stage renal disease patients is associated with significantly increased morbidity and mortality. The prevalence of pulmonary hypertension in dialysis patients is relatively high and varies in different studies from 17% to 49.53% depending on the mode of dialysis and other selection factors, such as the presence of other cardiovascular comorbidities. The etiopathogenic mechanisms that have been studied in relatively small studies mainly include arteriovenous fistula-induced increased cardiac output, which cannot be accomodated by, the spacious under normal conditions pulmonary circulation. Additionally, pulmonary vessels show signs of endothelial dysfunction, dysregulation of vascular tone due to an imbalance in vasoactive substances, and local as well as systemic inflammation. It is also believed that microbubbles escaping from the dialysis circuit can trigger vasoconstriction and vascular sclerosis. The non-specific therapeutic options that proved to be beneficial in pulmonary artery pressure reduction are endothelin inhibitors, phosphodiesterase inhibitor sildenafil, and vasodilatory prostaglandins in various forms. The specific modes of treatment are renal transplantation, size reduction or closure of high-flow arteriovenous fistulas, and transfer from hemodialysis to peritoneal dialysis-a modality that is associated with a lesser prevalence of pulmonary hypertension.
  PMID: 23405977 [PubMed - as supplied by publisher]
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16. Eur J Pharmacol. 2013 Feb 8. pii: S0014-2999(13)00070-8. doi: 10.1016/j.ejphar.2013.01.050. [Epub ahead of print]

A novel Ca²(+) channel antagonist reverses cardiac hypertrophy and pulmonary arteriolar remodeling in experimental pulmonary hypertension.

Pereira SLKummerle AEFraga CABarreiro EJRocha NNFerraz EBNascimento JHSudo RTZapata-Sudo G.
Instituto de Ciências Biomédicas, Programa de Desenvolvimento de Fármacos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address:


This work investigates the actions of LASSBio-1289, (E)-N-methyl-N'-(thiophen-3-methylene)benzo[d][1,3]dioxole-5-carbohydrazide, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Two weeks following the MCT injection, LASSBio-1289 (50 or 75mg/kg, p.o.) or vehicle was administrated once daily for 14 days. LASSBio-1289 (75mg/kg) treatment caused a significant decrease in right ventricular systolic pressure (31.89±0.82mmHg) compared to the MCT-vehicle group (52.74±6.19mmHg; P<0.05). Oral treatment with LASSBio-1289 (50 or 75mg/kg) effectively decreased pulmonary artery diameter and right ventricle (RV) area, assessed by echocardiography. LASSBio-1289 (75mg/kg) reduced RV area (10.00±0.58mm(2)) compared to the MCT-vehicle group (20.50±1.44mm(2); P<0.05). LASSBio-1289 (75mg/kg) also partially recovered the pulmonary artery acceleration time in MCT-treated rats. Oral treatment with LASSBio-1289 (50mg/kg) decreased the pulmonary arteriolar wall thickness (68.57±2.21%) compared to the MCT-vehicle group (81.07±1.92%; P<0.05). In experiments with isolated pulmonary arteries, the concentration of LASSBio-1289 necessary to produce 50% relaxation in the phenylephrine- or KCl-induced contraction was 27.31±6.94 and 2.72±0.99μM, respectively, P<0.05. In the presence of LASSBio-1289 (50μM), the maximal contraction induced by 10mM CaCl(2) was reduced to 36.00±8.28% of the maximal contraction of the control curve (P<0.05). LASSBio-1289 was effective in attenuating MCT-induced PAH in rats, and its beneficial effects were likely mediated by the inhibition of extracellular Ca(2+) influx through L-type voltage-gated Ca(2+) channels in the pulmonary artery.
Copyright © 2013. Published by Elsevier B.V.
  PMID: 23399770 [PubMed - as supplied by publisher]
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17. Eur J Clin Microbiol Infect Dis. 2013 Feb 7. [Epub ahead of print]

Central venous catheter-related blood stream infections in patients receiving intravenous iloprost for pulmonary hypertension.

Sammut DElliot CAKiely DGArmstrong IJMartin LWilkinson JSephton PJones JHamilton NHurdman J,McLellan ESabroe ICondliffe R.
Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, S10 2JF, UK.


Catheter-related blood stream infection (CR-BSI) in patients with pulmonary hypertension (PH) receiving intravenous iloprost via an indwelling central line has previously not been fully described. Recent studies have suggested a link between the pH of prostanoid infusions and the rate and nature of CR-BSI. We have investigated CR-BSI in patients receiving intravenous iloprost at our unit. Databases and hospital records were interrogated for all patients receiving intravenous iloprost between September 2007 and June 2012. Fifty-nine patients received intravenous iloprost via an indwelling central catheter with a total of 23,072 treatment days. There were 15 episodes of CR-BSI, identified using a systematic screening protocol, involving 11 patients giving an overall CR-BSI rate of 0.65/1,000 treatment days. CR-BSI rate for Gram-positive organisms was 0.26/1,000 treatment-days and for Gram-negative organisms was 0.39/1,000 treatment-days. The pH of iloprost in typical dosing regimens was comparable to the pH used in standard-diluent treprostinil and dissimilar to alkaline epoprostenol infusions. The proportion of Gram-negative CR-BSI was similar to that reported for standard-diluent treprostinil. CRP was normal on admission in 33 % of cases of confirmed CR-BSI and remained normal in 13 % of cases. CR-BSI rates with intravenous iloprost are comparable to those observed for other prostanoids. The high proportion of Gram-negative organisms observed and the neutral pH of iloprost infusions support the previously hypothesised link between pH and antimicrobial activity. Although usually elevated during a CR-BSI, CRP may be normal in early infection and a normal result cannot completely exclude infection.
  PMID: 23388830 [PubMed - as supplied by publisher]
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18. J Invasive Cardiol. 2013 Feb;25(2):89-91.

Acute Hand Ischemia After Radial Intervention in Patient With CREST-Associated Pulmonary Hypertension: Successful Treatment With Manual Thromboaspiration.

Taglieri NGaliè NMarzocchi A.
Institute of Cardiology, Bologna University, St Orsola/Malpighi Hospital, Via Massarenti 9, 40138, Bologna,


We describe the case of a 60-year-old woman with CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) associated pulmonary hypertension undergoing transradial coronary angiography. The day after the procedure, the patient complained of severe symptoms and signs of acute hand ischemia. Urgent right upper extremity angiography showed the lack of ulnar palmar arch and a severe narrowed radial artery with endoluminal filling defect. The patient was successfully treated with manual thromboaspiration leading to a complete flow restoration and symptom relief. This case shows that radial occlusion, one of the most common and usually asymptomatic complications following transradial cardiac catheterization, may cause severe hand ischemia in patients with small-vessel inflammatory disease.
Free Article
  PMID: 23388228 [PubMed - in process]
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19. Obstet Gynecol. 2012 Dec;120(6):1283-90. doi: http://10.1097/AOG.0b013e3182733d56.

Maternal, perinatal, and postneonatal outcomes in women with chronic heart disease in Washington State.

Leary PJLeary SEStout KKSchwartz SMEasterling TR.
Department of Obstetrics and Gynecology and Divisions of Pulmonary and Critical Care Medicine and Cardiology, University of Washington Medical Center, Seattle, Washington 98195-6522, USA.



To explore the association between the presence of maternal heart disease and maternal, perinatal, and infant outcomes.


We conducted a population-based retrospective cohort study using Washington State birth certificates linked with hospital discharge records of mothers noted to have maternal congenital heart disease, ischemic heart disease, heart failure, or pulmonary hypertension. Women who gave birth between 1987 and 2009 (n=2,171) were compared with a sample of mothers without these conditions (n=21,710). We described characteristics of pregnant women with heart disease over time. Logistic regression estimated the association between chronic maternal heart disease and small-for-gestational-age (SGA) neonates as well as perinatal, postneonatal, and maternal death.


The proportion of births to women with reported heart disease increased 224% between the 1987 and 1994 and 2002 and 2009 calendar periods. Chronic maternal heart disease was associated with increased risk of SGA (62 additional SGA newborns per 1,000 births, 95% confidence interval [CI] 46-78; P<.001), perinatal death (14 additional deaths per 1,000 births, 95% CI 8-20; P<.001), postneonatal death (5 additional deaths per 1,000 births, 95% CI 2-9; P<.001), and maternal death (5 additional deaths per 1,000 births, 95% CI 2-9; P<.001).


The presence of chronic maternal heart disease is associated with elevated risk for poor maternal, perinatal, and postneonatal outcomes.
  PMID: 23168751 [PubMed - indexed for MEDLINE]
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20. Radiology. 2013 Jan;266(1):114-22. doi: 10.1148/radiol.12111599. Epub 2012 Nov 14.

Regional and global biventricular function in pulmonary arterial hypertension: a cardiac MR imaging study.

Shehata MLHarouni AASkrok JBasha TABoyce DLechtzin NMathai SCGirgis ROsman NFLima JABluemke DAHassoun PMVogel-Claussen J.
Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe St, Nelson Basement MRI 110, Baltimore, MD 21287, USA.



To determine whether chronic pulmonary arterial pressure (PAP) elevation affects regional biventricular function and whether regional myocardial function may be reduced in pulmonary arterial hypertension (PAH) patients with preserved global right ventricular (RV) function.


After informed consent, 35 PAH patients were evaluated with right heart catheterization and cardiac magnetic resonance (MR) imaging and compared with 13 healthy control subjects. Biventricular segmental, section, and mean ventricular peak systolic longitudinal strain (E(LL)), as well as left ventricular (LV) circumferential and RV tangential strains were compared between PAH patients and control subjects and correlated with global function and catheterization of the right heart indexes. Spearman ρ correlation with Bonferroni correction was used. Multiple linear regression analysis was performed to determine predictors for regional myocardial function.


In the RV of PAH patients, longitudinal contractility was reduced at the basal, mid, and apical levels, and tangential contractility was reduced at the midventricular level. Mean RV E(LL) positively correlated with mean PAP (r = 0.62, P < .0014) and pulmonary vascular resistance index (PVRI) (r = 0.77, P < .0014). Mean PAP was a predictor of mean RV E(LL) (β = .19, P = .005) in a multiple linear regression analysis. In the LV, reduced LV longitudinal and circumferential contractility were noted at the base. LV anteroseptal E(LL) positively correlated with increased mean PAP (r = 0.5, P = .03) and septal eccentricity index (r = 0.5, P = .01). In a subgroup of PAH patients with normal global RV function, significantly reduced RV longitudinal contractility was noted at basal and mid anterior septal insertions, as well as the mid anterior RV wall (P < .05 for all).


In PAH patients, reduced biventricular regional function is associated with increased RV afterload (mean PAP and PVRI). Cardiac MR imaging helps identify regional RV dysfunction in PAH patients with normal global RV function.

RSNA, 2012
PMCID: PMC3528967 [Available on 2014/1/1]
  PMID: 23151825 [PubMed - indexed for MEDLINE]
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21. Int J Clin Pract Suppl. 2012 Oct;(177):2-4. doi: 10.1111/j.1742-1241.2012.03011.x.

Moving beyond stigma--are concurrent palliative care and management of pulmonary arterial hypertension irreconcilable or future best practice?

Kimeu AKSwetz KM.
Division of General Internal Medicine, Department of Medicine, Section of Palliative Medicine, Mayo Clinic, Rochester, MN, USA.
  PMID: 22943512 [PubMed - indexed for MEDLINE]
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22. Biochem Biophys Res Commun. 2012 Oct 5;426(4):486-91. doi: 10.1016/j.bbrc.2012.08.106. Epub 2012 Aug 28.

Viral Toll Like Receptor activation of pulmonary vascular smooth muscle cells results in endothelin-1 generation; relevance to pathogenesis of pulmonary arterial hypertension.

George PMBadiger RShao DEdwards MRWort SJPaul-Clark MJMitchell JA.
Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London, United Kingdom.


Pulmonary arterial hypertension (PAH) is a rare but fatal condition in which raised pulmonary vascular resistance leads to right heart failure and death. Endothelin-1 is a potent endogenous vasoconstrictor, which is considered to be central to many of the events that lead to PAH, and is an important therapeutic target in the treatment of the condition. In many cases of PAH, the aetiology is unknown but inflammation is increasingly thought to play an important role and viruses have been implicated in the development of disease. The Toll Like Receptors (TLRs) play a key role in innate immune responses by initiating specific anti-bacterial and anti-viral defences in recognition of signature molecular motifs on the surface of invading pathogens. In this study, we set out to examine the expression of bacterial and viral TLRs in human pulmonary artery smooth muscle cells and to establish whether their activation could be relevant to PAH. We found that the viral TLR3 and bacterial TLRs 4 and 6 were most abundantly expressed in human pulmonary artery smooth muscle cells. Using specific TLR ligands, we found that activation of TLRs 3 and 4 resulted in IL-8 release by human pulmonary artery smooth muscle cells but that only TLR3 stimulation resulted in IP10 and endothelin-1 release. These data suggest that human pulmonary artery smooth muscle cells express significant levels of viral TLR3 and respond to its activation by releasing endothelin-1. This may have importance in understanding the association between viruses and the development of PAH.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 22960172 [PubMed - indexed for MEDLINE]
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23. Lung. 2012 Oct;190(5):573-8. Epub 2012 Jul 15.

Transition of PH patients from sildenafil to tadalafil: feasibility and practical considerations.

Shlobin OABrown AWWeir NAhmad SLemma MNathan SD.
Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA.



Sildenafil was the only phosphodiesterase-5 inhibitor available for the treatment of pulmonary arterial hypertension (PAH) until the approval and availability of once-daily tadalafil. Since no direct comparative study is likely to be performed between these agents, we sought to evaluate the feasibility of transitioning stable PAH patients from sildenafil to tadalafil.


The primary end point was continuation on tadalafil without clinical deterioration. A functional outcome through an evaluation of serial change in the 6-min walk test distance (6MWD) was also performed.


Thirty-five patients on sildenafil qualified for the analysis, of which 85.7 % (30/35) were successfully transitioned. The remaining 14.3 % (5/30) (failure group) were switched back to sildenafil due to worsening symptoms. The mean pretransition 6MWD was 363 m, with an average change in the success group of +16.4 m (range = -64 to +140 m) compared to -45 m (range = -123 to +32 m) in the failure group at 1-3 months post switch (p = 0.02). All 30 patients in the success group remained on tadalafil, with an average improvement in the 6MWD of +37.04 m (range = -36.5 to +236.5 m) at 12 months post switch. The failure group had a higher daily sildenafil dose (180 vs. 115.5 mg; p = 0.06), with 42.8 % of patients at the highest sildenafil dose failing the transition.


The transition from sildenafil to tadalafil is safe and generally well tolerated. Patients with more severe disease and those on higher doses of sildenafil are more likely to fail the transition and should be monitored closely post switch.
  PMID: 22797830 [PubMed - indexed for MEDLINE]
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24. J Clin Anesth. 2012 Sep;24(6):487-9. doi: 10.1016/j.jclinane.2012.02.005. Epub 2012 Jul 2.

Scheduled perioperative switch from oral sildenafil to intravenous epoprostenol in a patient with Eisenmenger syndrome undergoing a sigmoidectomy.

Moriyama KUzawa KIijima TKotani MMoriyama KOhashi YSatoh TYorozu T.
Department of Anesthesiology, Kyorin University Faculty of Medicine, Tokyo 181-8611, Japan.


The perioperative management of pulmonary hypertension in a patient with Eisenmenger syndrome, the most advanced form of associated pulmonary artery hypertension (PAH), who required a sigmoidectomy is presented. The treatment for pulmonary hypertension was switched from oral sildenafil to intravenous epoprostenol to avoid the unexpected discontinuation of vasodilation during the perioperative period. The scheduled perioperative conversion should be considered for patients with severe PAH undergoing major abdominal surgery to ensure the stabilization of pulmonary and systemic hemodynamics.
Copyright © 2012 Elsevier Inc. All rights reserved.
  PMID: 22762976 [PubMed - indexed for MEDLINE]
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25. Am J Cardiol. 2013 Jan 1;111(1):143-8. doi: 10.1016/j.amjcard.2012.08.061. Epub 2012 Oct 23.

Role of serial quantitative assessment of right ventricular function by strain in pulmonary arterial hypertension.

Hardegree ELSachdev AVillarraga HRFrantz RPMcGoon MDKushwaha SSHsiao JFMcCully RBOh JK,Pellikka PAKane GC.
Mayo School of Graduate Medical Education, Rochester, MN, USA.


The aim of this study was to assess whether serial quantitative assessment of right ventricular (RV) function by speckle-based strain imaging is affected by pulmonary hypertension-specific therapies and whether there is a correlation between serial changes in RV strain and clinical status. RV longitudinal systolic function was assessed using speckle-tracking echocardiography in 50 patients with pulmonary arterial hypertension (PAH) before and after the initiation of therapy. The mean interval to follow-up was 6 ± 2 months. Subsequent survival was assessed over 4 years. Patients demonstrated a mean increase in RV systolic strain from -15 ± 5 before to -20 ± 7% (p = 0.0001) after PAH treatment. Persistence of or progression to a severe reduction in free wall systolic strain (<-12.5%) at 6 months was associated with greater disease severity (100% were in functional class III or IV vs 42%, p = 0.005), greater diuretic use (86% vs 40%, p = 0.02), higher mean pulmonary artery pressure (67 ± 20 vs 46 ± 17 mm Hg, p = 0.006), and poorer survival (4-year mortality 43% vs 23%, p = 0.002). After adjusting for age, functional class, and RV strain at baseline, patients with ≥ 5% improvement in RV free wall systolic strain had a greater than sevenfold lower mortality risk at 4 years (hazard ratio 0.13, 95% confidence interval 0.03 to 0.50, p = 0.003). In conclusion, serial echocardiographic assessment of RV longitudinal systolic function by quantitative strain imaging independently predicts clinical deterioration and mortality in patients with PAH after the institution of medical therapy.
Copyright © 2013. Published by Elsevier Inc.
  PMID: 23102474 [PubMed - indexed for MEDLINE]
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26. Eur Respir J. 2013 Feb 8. [Epub ahead of print]

Chronic Thromboembolic Pulmonary Hypertension: Role of medical therapy.

Pepke-Zaba JJansa PKim NHNaejie RSimonneau G.
Papworth Hospital, Cambridge, UK.


Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease with poor prognosis if not treated. The treatment of choice is surgery with pulmonary endarterectomy. However, a significant percentage of patients are deemed non-operable due to distal distribution of the disease and arteriopathy in the non-occluded areas that is indistinguishable from pulmonary arterial hypertension (PAH). The overlap in clinical presentation, pathological features and pathogenesis between PAH and CTEPH provides a compelling rationale for exploring the efficacy of PAH-targeted therapies in CTEPH. These therapies are often considered for non-operable patients and are also used in operable patients as a bridge to surgery or as post-PEA therapy for persistent pulmonary hypertension, despite the fact they are not licensed for CTEPH.Two randomised clinical trials (RCTs) have been performed in non-operable CTEPH patients. The BENEFiT study, with the endothelin receptor antagonist bosentan, did not show improvement in walking distance. Recently, the CHEST-1 trial, with the soluble guanylate cyclase stimulator riociguat, met study endpoint and demonstrated significant improvement in walking distance in patients with non-operable CTEPH.There is an urgent need for more RCTs designed to clarify whether administration of PAH-targeted therapies improves clinically meaningful endpoints in various CTEPH populations.
  PMID: 23397304 [PubMed - as supplied by publisher]
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27. Eur Respir J. 2013 Feb 8. [Epub ahead of print]

Pulmonary hypertension in antisynthetase syndrome: prevalence, etiology and survival.

Hervier BMeyer ADieval CUzunhan YDevilliers HLaunay DCanuet MTêtu LAgard CSibilia JHamidou M,Amoura ZNunes HBenveniste OGrenier PMontani DHachulla E.
APHP, Paris, France & University of Paris VI Pierre & Marie Curie; Internal Medicine dept 2 & INSERM UMRS-945, French Reference Center for Lupus.


Antisynthetase syndrome (ASS) is characterized by the association of interstitial lung disease (ILD) and myositis with different anti-tRNA-synthetase antibodies. The occurrence, etiology and prognosis of pulmonary hypertension (PH) have not yet been evaluated.Among 203 consecutive patients, echocardiography (TTE) and right heart catheterization (RHC) results were retrospectively analysed in light of clinico-biological, morphological and functional parameters. Definitions of PH were based on the ESC/ERS 2009 guidelines, severe PH being defined by a mean pulmonary arterial pressure (mPAP) >35 mmHg.PH was suspected by TTE in 47 (23.2%) cases, corresponding to PH "possible" (n=27, 13.3%) or "likely" (n=20, 9.9%). RHC was performed in 21 patients, excluding PH in 5 and confirming pre-capillary PH in 16 (7.9%). Although related to ILD in all cases, pre-capillary PH was severe in 13 (81,3%) patients (mean mPAP: 46±9 mmHg), frequently associated with low cardiac index (mean 2.3±0.8 l·min(-1)·m(-2)) and high FVC/DL,CO ratio (2.5±0.6). PH was clearly associated with a lower survival (p<0.001), with a 3-year survival rate of 58%.The occurrence of PH in ASS is significant and dramatically worsens the prognosis. Although systematically associated with ILD, PH was usually severe, suggesting a specific pulmonary vascular involvement.
  PMID: 23397301 [PubMed - as supplied by publisher]
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28. J Nucl Cardiol. 2013 Jan 26. [Epub ahead of print]

Evaluation of right ventricular volume and ejection fraction by gated (18)F-FDG PET in patients with pulmonary hypertension: Comparison with cardiac MRI and CT.

Wang LZhang YYan CHe JXiong CZhao SFang W.
Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 Beilishi Road, Beijing, 100037, China.



Right ventricular (RV) function is a powerful predictor of survival in patients with pulmonary hypertension (PH), but noninvasively assessing RV function remains a challenge. The aim of this study was to prospectively compare gated (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) myocardial imaging (gated PET), cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) for the assessment of RV volume and ejection fraction in patients with PH.


Twenty-three consecutive patients aged more than 16 years diagnosed with PH were included. All patients underwent gated PET, CMR, and CCT within 7 days. Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), and right ventricular ejection fraction (RVEF) were calculated by three imaging modalities. RV (18)F-FDG uptake was determined as RV-corrected standardized uptake value (SUV), and the ratio of RV to left ventricular (LV)-corrected SUV (Corrected SUV R/L).


Gated PET showed a moderate correlation (r = 0.680, P < .001) for RVEDV, good correlation for RVESV (r = 0.757, P < .001) and RVEF (r = 0.788, P < .001) with CMR, and good correlation for RVEDV (r = 0.767, P < .001), RVESV (r = 0.837, P < .001), and RVEF (r = 0.730, P < .001) with CCT. Bland-Altman analysis revealed systematic underestimation of RVEDV and RVESV and overestimation of RVEF with gated PET compared with CMR and CCT. The correlation between RVESV (r = 0.863, P < .001), RVESV (r = 0.903, P < .001), and RVEF (r = 0.853, P < .001) of CMR and those of CCT was excellent; Bland-Altman analysis showed only a slight systematic variation between CMR and CCT. There were statistically significant negative correlations between RV-corrected SUV and RVEF-CMR (r = -0.543, P < .01), Corrected SUV R/L and RVEF-CMR (r = -0.521, P < .05), RV-corrected SUV and RVEF-CCT (r = -0.429, P < .05), Corrected SUV R/L and RVEF-CCT (r = -0.580, P < .01), respectively.


Gated PET had moderate-to-high correlation with CMR and CCT in the assessments of RV volume and ejection fraction. It is an available method for simultaneous assessing of RV function and myocardial glucose metabolism in patients with PH.
  PMID: 23354658 [PubMed - as supplied by publisher]
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29. Am Heart J. 2013 Feb;165(2):200-7. doi: 10.1016/j.ahj.2012.10.020. Epub 2012 Nov 28.

Clinical and echocardiographic correlations of exercise-induced pulmonary hypertension in systemic sclerosis: A multicenter study.

Gargani LPignone AAgoston GMoreo ACapati EBadano LPDoveri MBazzichi LCostantino MFPavellini APieri FMusca FMuraru DEpis OBruschi EDe Chiara BPerfetto FMori FParodi OSicari RBombardieri SVarga A,Cerinic MMBossone EPicano E.
Institute of Clinical Physiology, National Council of Research, Pisa, Italy. Electronic address:



Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation.


The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc.


We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively.


Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR.


Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.
Copyright © 2013 Mosby, Inc. All rights reserved.
  PMID: 23351823 [PubMed - in process]
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30. ASAIO J. 2012 Sep-Oct;58(5):526-9. doi: 10.1097/MAT.0b013e31826417d8.

Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

Shafii AEMason DPBrown CRVakil NJohnston DRMcCurry KRPettersson GBMurthy SC.
Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Comment in

Extracorporeal membrane oxygenation as a bridge to lung transplantation.Cypel M, Keshavjee S. ASAIO J. 2012 Sep-Oct; 58(5):441-2.


Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.
  PMID: 22929896 [PubMed - indexed for MEDLINE]
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31. Am J Respir Crit Care Med. 2013 Jan 24. [Epub ahead of print]

Exercise Induced Pulmonary Hypertension Physiological Basis and Methodological Concerns.

Naeije RVanderpool RDhakal BPSaggar RSaggar RVachiery JLLewis GD.
PH Clinic, Cardiology, Erasme Academic Hospital, Brussels, Belgium.


Exercise stresses the pulmonary circulation through increases in cardiac output and left atrial pressure. Invasive as well as non-invasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure-flow relationships ranges from 0.5 to 3 mmHg.L.min-1. The upper limit of normal of mean pulmonary artery pressure at exercise thus approximates 30 mmHg at a cardiac output of less than 10 L.min-1, or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to pulmonary artery pressure in a close to one for one mmHg fashion. Multipoint pulmonary artery pressure-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity which is explained by resistive vessel distensibility. When mean pulmonary artery pressure is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase cardiac output at the highest levels of exercise. Exercise has to be dynamic, to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Post-exercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in pulmonary artery pressure to a mean higher than 30 mmHg may be associated with dyspnea-fatigue symptomatology.
  PMID: 23348976 [PubMed - as supplied by publisher]
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32. Thorax. 2013 Jan 24. doi: 10.1136/thoraxjnl-2012-203020. [Epub ahead of print]

3D contrast-enhanced lung perfusion MRI is an effective screening tool for chronic thromboembolic pulmonary hypertension: results from the ASPIRE Registry.

Rajaram SSwift AJTelfer AHurdman JMarshall HLorenz ECapener DDavies CHill CElliot CCondliffe RWild JMKiely DG.
Academic Unit of Radiology, University of Sheffield, , Sheffield, UK.



Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism potentially curable by surgery. Perfusion scintigraphy is currently advocated as the imaging modality of choice to exclude CTEPH due to its high sensitivity. We have evaluated the diagnostic utility of lung perfusion MRI.


Consecutive patients attending a pulmonary hypertension referral centre undergoing lung perfusion MRI, perfusion scintigraphy, CT pulmonary angiography (CTPA) and right heart catheterisation within 14 days were identified.


Of 132 patients, 78 were diagnosed as having CTEPH. Lung perfusion MRI correctly identified 76 patients as having CTEPH with an overall sensitivity of 97%, specificity 92%, positive predictive value 95% and negative predictive value 96% compared with perfusion scintigraphy (sensitivity 96%, specificity 90%) and CTPA (sensitivity 94%, specificity 98%). No cases of surgically accessible CTEPH were missed with either modality.


Lung perfusion MRI has high sensitivity equivalent to perfusion scintigraphy in diagnosing CTEPH but does not require ionising radiation, making it an attractive initial imaging modality to assess patients with suspected CTEPH.
  PMID: 23349220 [PubMed - as supplied by publisher]
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33. Sleep Med. 2013 Jan 19. pii: S1389-9457(12)00437-6. doi: 10.1016/j.sleep.2012.11.013. [Epub ahead of print]

Sleep apnea in precapillary pulmonary hypertension.

Dumitrascu RTiede HEckermann JMayer KReichenberger FGhofrani HASeeger WHeitmann JSchulz R.
University of Giessen Lung Center, Germany.



Pilot studies have described the occurrence of sleep apnea in patients with precapillary pulmonary hypertension (PH). However, there are no data on the prevalence of sleep-related breathing disorders in larger patient cohorts with PH.


169 patients with a diagnosis of PH confirmed by right heart catheterisation and clinically stable in NYHA classes II or III were prospectively investigated by polygraphy (n=105 females, mean age: 61.3years, mean body mass index: 27.2kg/m(2)). Recruitment was independent of sleep-related symptoms and the use of vasodilator drugs or nasal oxygen.


45 patients (i.e. 26.6%) had an apnea-hypopnea-index (AHI) >10/h. Of these, 27 patients (i.e. 16%) had obstructive sleep apnea (OSA) and 18 patients (i.e. 10.6%) had central sleep apnea (CSA). The mean AHI was 20/hour. As a polygraphy had been performed with nasal oxygen in half of the patients without evidence for sleep apnea, the frequency of CSA was probably underestimated. Patients with OSA were characterized by male gender and higher body mass index whereas, those with CSA were older and hypocapnic.


At least every fourth patient with PH suffers from mild-to-moderate sleep apnea. Considering the anthropometric characteristics of the patients studied, the prevalence of both OSA and CSA seem to be higher in PH than in the general population.
Copyright © 2012 Elsevier B.V. All rights reserved.
  PMID: 23340085 [PubMed - as supplied by publisher]
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34. Eur Respir Rev. 2012 Sep 1;21(125):259-62. doi: 10.1183/‚Äč09059180.00003612.

Treat-to-target approach in pulmonary arterial hypertension: a consensus-based proposal.

Sitbon OBaloira Villar ABauer FEkmehag BGin-Sing WJansson KKiely DGLeuchte HManes A,Rosenkranz SEscribano P. Free Article
  PMID: 22941892 [PubMed - indexed for MEDLINE]
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35. Eur Respir Rev. 2012 Sep 1;21(125):234-8. doi: 10.1183/09059180.00003712.

The study of risk in pulmonary arterial hypertension.

Rubin LJSimonneau GBadesch DGaliè NHumbert MKeogh AMassaro JMatucci Cerinic MSitbon O,Kymes S.
School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.


A growing body of published evidence exists on the risk factors for disease progression in pulmonary arterial hypertension (PAH). The Scientific Steering Committee for the Study of Risk in PAH was established to bring together leading clinical and statistical experts in PAH and risk modelling, for the purpose of advancing the understanding of the risk of development and progression of PAH. Herein, we discuss the impact of this information on three key areas: 1) clinical decision-making; 2) policy and reimbursement; and 3) future trials and research.
Free Article
  PMID: 22941888 [PubMed - indexed for MEDLINE]
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36. Eur Respir Rev. 2012 Sep 1;21(125):223-33. doi: 10.1183/09059180.00007211.

Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview.

Porres-Aguilar MAltamirano JTTorre-Delgadillo ACharlton MRDuarte-Rojo A.
Dept of Internal Medicine, Division of Hospital Medicine, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, TX, USA.


Liver disease and portal hypertension can be associated with pulmonary vascular complications, including portopulmonary hypertension (POPH), characterised by an elevated mean pulmonary artery pressure secondary to an increased pulmonary vascular resistance, and hepatopulmonary syndrome (HPS), characterised by hypoxaemia due to pulmonary vasodilatation and shunting. Although clear diagnostic guidelines exist for both conditions on the basis of echocardiography, right heart catheterisation and arterial blood gases, there is considerable variation between centres regarding diagnosis and management of these conditions. Awareness of evaluation and management algorithms for POPH and HPS are critical for optimisation of outcomes in patients with these conditions. Key aspects of management of POPH and HPS include identification of patients likely to benefit from liver transplantation (LTx) and management before and after LTx. Although both disorders may improve after LTx, severe forms of POPH represent a contraindication to LTx. Novel approaches to the treatment of POPH and HPS offer new management options that may expand the pool of transplantable patients and improve overall outcomes.
Free Article
  PMID: 22941887 [PubMed - indexed for MEDLINE]
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37. Eur Respir Rev. 2012 Sep 1;21(125):218-22. doi: 10.1183/09059180.00003512.

A critical analysis of survival in pulmonary arterial hypertension.

O'Callaghan DSHumbert M.
Centre for Lung Health, Mater Misericordiae University Hospital, Dublin, Ireland.


Pulmonary arterial hypertension (PAH) is a rare disease characterised by a progressive increase in pulmonary vascular resistance, leading to right heart failure and premature death. Over the last two decades, a better understanding of the pathogenesis of PAH has led to the approval of several targeted therapies that confer improvements in patients' clinical and haemodynamic status, quality of life and survival. Analysis of recent survival data in PAH cohorts have been biased by the inclusion of prevalent patients included months or years after PAH diagnosis ("survivors") who have a better prognosis than corresponding incident patients diagnosed at the time of recruitment. A critical analysis of recent multicentre incident cohorts has shown survival improvements in the current management era. However, idiopathic PAH remains a severe disease and still carries a poor prognosis. Modern survival figures also highlight the relevance of lung transplantation in eligible PAH patients who are refractory to current best standard of medical care.
Free Article
  PMID: 22941886 [PubMed - indexed for MEDLINE]
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38. J Pharmacol Exp Ther. 2012 Dec;343(3):547-55. doi: 10.1124/jpet.112.197152. Epub 2012 Aug 23.

Differential effects of Selexipag [corrected] and prostacyclin analogs in rat pulmonary artery.

Morrison KStuder RErnst RHaag FKauser KClozel M.
Drug Discovery Department, Actelion Pharmaceuticals Ltd., Switzerland.

Erratum in

  • J Pharmacol Exp Ther. 2013 Jan;344(1):317.


{4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (ACT-333679) is the main metabolite of the selective prostacyclin (PGI(2)) receptor (IP receptor) agonist selexipag. The goal of this study was to determine the influence of IP receptor selectivity on the vasorelaxant efficacy of ACT-333679 and the PGI(2) analog treprostinil in pulmonary artery under conditions associated with pulmonary arterial hypertension (PAH). Selexipag and ACT-333679 evoked full relaxation of pulmonary artery from control and monocrotaline (MCT)-PAH rats, and ACT-333679 relaxed normal pulmonary artery contracted with either endothelin-1 (ET-1) or phenylephrine. In contrast, treprostinil evoked weaker relaxation than ACT-333679 of control pulmonary artery and failed to induce relaxation of pulmonary artery from MCT-PAH rats. Treprostinil did not evoke relaxation of normal pulmonary artery contracted with either ET-1 or phenylephrine. Expression of prostaglandin E(3) (EP(3)) receptor mRNA was increased in pulmonary artery from MCT-PAH rats. In contraction experiments, the selective EP(3) receptor agonist sulprostone evoked significantly greater contraction of pulmonary artery from MCT-PAH rats compared with control rats. The presence of a threshold concentration of ET-1 significantly augmented the contractile response to sulprostone in normal pulmonary artery. ACT-333679 did not evoke direct contraction of rat pulmonary artery, whereas treprostinil evoked concentration-dependent contraction that was inhibited by the EP(3) receptor antagonist (2E)-3-(3',4'-dichlorobiphenyl-2-yl)-N-(2-thienylsulfonyl)acrylamide. Antagonism of EP(3) receptors also revealed a relaxant response to treprostinil in normal pulmonary artery contracted with ET-1. These data demonstrate that the relaxant efficacy of the selective IP receptor agonist selexipag and its metabolite ACT-333679 is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease.
  PMID: 22918043 [PubMed - indexed for MEDLINE]
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39. J Vasc Nurs. 2012 Sep;30(3):94-7. doi: 10.1016/j.jvn.2012.02.001.

Irreversible sequela in an arterial venous fistula with steal syndrome: a case study.

Raml NM.
Department of Vascular Surgery, Zablocki VA Medical Center and Marquette University College of Nursing, Milwaukee, Wisconsin 53295, USA.


Arteriovenous fistulas may be susceptible to steal syndrome from a variety of conditions. Steal syndrome is defined as arterial insufficiency distal to the arteriovenous fistula. The causality of the insufficiency may include arterial disease proximal or distal to the fistula, markedly high blood flow volume after creation, or undetected collateral flow. Prior arterial disease may expose insufficient profusion to the distal extremity after fistula creation. High blood flow volume immediately after fistula creation may perhaps cause steal syndrome symptoms, but this often resolves with fistula maturation. Undetected collateral flow, or side branches, from target vessels receive increased blood volume after fistula creation and expand, thereby stealing blood flow from the hand. This particular condition can potentially cause ischemic changes distal to the fistula with potentially irreversible sequela if not recognized in a timely manner. A sixty- one year old male, sent with chest pain to the emergency room from his dialysis center, was found to have steal syndrome with an accompanying motor deficit. The diagnosis of steal syndrome is based on physical examination, patient history, and confirmation testing such as doppler ultrasound, digital pressures or arteriogram. A thorough preoperative workup and careful postoperative monitoring can minimize steal syndrome and prevent permanent impairment.
Published by Mosby, Inc.
  PMID: 22901448 [PubMed - indexed for MEDLINE]
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40. Pharmacotherapy. 2012 Sep;32(9):838-55. doi: 10.1002/j.1875-9114.2012.01114.x. Epub 2012 Jul 17.

Practical considerations for the pharmacotherapy of pulmonary arterial hypertension.

Bishop BMMauro VFKhouri SJ.
Colleges of Pharmacy and Pharmaceutical Sciences, Toledo, OH 43614, USA.


Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.
© 2012 Pharmacotherapy Publications, Inc. All rights reserved.
  PMID: 22806762 [PubMed - indexed for MEDLINE]
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41. J Pediatr. 2012 Dec;161(6):1126-31. doi: 10.1016/j.jpeds.2012.05.050. Epub 2012 Jun 28.

Tissue Doppler imaging predicts adverse outcome in children with idiopathic pulmonary arterial hypertension.

Takatsuki SNakayama TJone PNWagner BDNaoi KIvy DDSaji T.
Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.



To evaluate the clinical utility of tissue Doppler imaging (TDI) in assessment of disease severity and prognostic value in children with idiopathic pulmonary arterial hypertension (PAH).


A prospective study was performed to evaluate TDI velocities (systolic myocardial velocity, early diastolic myocardial relaxation velocity [Em], late diastolic myocardial velocity associated with atrial contraction), brain natriuretic peptide, New York Heart Association (NYHA) functional class, and hemodynamics in 51 children (mean age; 11.6 years) with idiopathic PAH. Fifty-one healthy children with comparable demographics served as controls.


Em, Em/late diastolic myocardial velocity associated with atrial contraction ratio, and systolic myocardial velocity at mitral annulus, septum, and tricuspid annulus in PAH were significantly reduced compared with controls. Tricuspid Em had significant inverse correlations with plasma brain natriuretic peptide levels (r = -0.60, P < .001), right ventricular end-diastolic pressure (r = -0.79, P < .001), and mean pulmonary arterial pressure (r = -0.67, P < .001). Statistically significant differences were observed in tricuspid Em between NYHA functional class II vs combined III and IV (mean and SD; 11.9 ± 4.2 cm/s vs 8.2 ± 3.6 cm/s, respectively, P = .002). Cumulative event-free survival rate was significantly lower when tricuspid Em was ≤8 cm/s (log-rank test, P < .001)


Tricuspid Em velocity correlated with NYHA functional class as disease severity and may serve as a useful prognostic marker in children with idiopathic PAH. The present study is the initial report to evaluate TDI velocities against midterm outcome variables in a relatively large pediatric PAH population.
Copyright © 2012 Mosby, Inc. All rights reserved.
PMCID: PMC3508005 [Available on 2013/12/1]
  PMID: 22748515 [PubMed - indexed for MEDLINE]
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42. Eur J Cardiothorac Surg. 2013 Jan 22. [Epub ahead of print]

Use of centrifugal left ventricular assist device as a bridge to candidacy in severe heart failure with secondary pulmonary hypertension.

Kutty RSParameshwar JLewis CCatarino PASudarshan CDJenkins DPDunning JJTsui SS.
Department of Cardiothoracic Surgery, The Transplant Unit, Papworth Hospital, Cambridge, UK.



Raised pulmonary artery pressure (PAP), trans-pulmonary gradient (TPG) and pulmonary vascular resistance (PVR) are risk factors for poor outcomes after heart transplant in patients with secondary pulmonary hypertension (PH) and may contraindicate transplant. Unloading of the left ventricle with an implantable left ventricular assist device (LVAD) may reverse these pulmonary vascular changes. We studied the effect of implanting centrifugal LVADs in a cohort of patients with secondary PH as a bridge to candidacy.


Pulmonary haemodynamics on patients implanted with centrifugal LVADs at a single unit between May 2005 and December 2010 were retrospectively reviewed.


Twenty-nine patients were implanted with centrifugal LVADs (eight HeartWare ventricular assist device (HVAD), HeartWare International, USA and 21 VentrAssist, Ventracor Ltd., Australia). Seventeen were ineligible for transplant by virtue of high TPG/PVR. All the patients were optimized with inotrope/balloon pump followed by LVAD insertion. Four required temporary right VAD support. Thirty-day mortality post-LVAD was 3.4% (1 of 29) with a 1-year survival of 85.7% (24 of 28). Thirteen patients have been transplanted to date: 30-day mortality was 7.7% (1 of 13) and 1-year survival was 91% (10 of 11). Baseline and post-VAD pulmonary haemodynamics were significantly improved: systolic PAP (mmHg), mean PAP, TPG (mmHg) of 57 ± 9.5, 42 ± 4.4 and 14 ± 3.9 reduced to 32 ± 7.5, 18 ± 5.5 and 9 ± 3.3, respectively. PVR reduced from 5 ± 1.5 to 2.1 ± 0.5 Wood units (P < 0.05).


In selected heart failure patients with secondary PH, use of centrifugal LVAD results in significant reductions in PAP, TPG and PVR, which are observed within 1 month, reaching a nadir by 3 months. Such patients bridged to candidacy have post-transplant survival comparable with those having a heart transplant as primary treatment.
  PMID: 23345184 [PubMed - as supplied by publish
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