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Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension

Show simple item record Morris C.R. Kim H.-Y. Wood J. Porter J.B. Klings E.S. Trachtenberg F.L. Sweeters N. Olivieri N.F. Kwiatkowski J.L. Virzi L. Singer S.T. Taher A. Neufeld E.J. Thompson A.A. Sachdev V. Larkin S. Suh J.H. Kuypers F.A. Vichinsky E.P.
dc.contributor.editor Sep-2013 2017-10-05T15:38:20Z 2017-10-05T15:38:20Z 2013
dc.identifier 10.3324/haematol.2012.082065
dc.identifier.issn 03906078
dc.description.abstract Pulmonary hypertension is a common but often overlooked complication associated with thalassemia syndromes. There are limited data on the safety and efficacy of selective pulmonary vasodilators in this at-risk population. We, therefore, designed a 12-week, open-label, phase 1-2, pilot-scale, proof-of-principle trial of sildenafil therapy in 10 patients with β-thalassemia and at increased risk of pulmonary hypertension based on an elevated tricuspid regurgitant jet velocity 2.5 m-s on Doppler-echocardiography. Variables compared at baseline and after 12 weeks of sildenafil treatment included Doppler-echocardiographic parameters, 6-minute walked distance, Borg Dyspnea Score, New York Heart Association functional class, pulmonary function, and laboratory parameters. Treatment with sildenafil resulted in a significant decrease in tricuspid regurgitant jet velocity by 13.3percent (3.0±0.7 versus 2.6±0.5 m-s, P=0.04), improved left ventricular end systolic-diastolic volume, and a trend towards a improved New York Heart Association functional class. No significant change in 6-minute walked distance was noted. Sildenafil was well tolerated, although minor expected adverse events were commonly reported. The total dose of sildenafil (mg) was strongly correlated with percent change in nitric oxide metabolite concentration in the plasma (ρ=0.80, P=0.01). There were also significant increases in plasma and erythrocyte arginine concentrations. Our study suggests that sildenafil is safe and may improve pulmonary hemodynamics in patients at risk of pulmonary hypertension; however, it was not demonstrated to improve the distance walked in 6 minutes. Clinical trials are needed to identify the best treatment strategy for pulmonary hypertension in patients with β-thalassemia. ( identifier: NCT00872170). © 2013 Ferrata Storti Foundation.
dc.format.extent Pages: (1359-1367)
dc.language English
dc.publisher PAVIA
dc.relation.ispartof Publication Name: Haematologica; Publication Year: 2013; Volume: 98; no. 9; Pages: (1359-1367);
dc.source Scopus
dc.title Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension
dc.type Article
dc.contributor.affiliation Morris, C.R., Department of Pediatrics, Division of Emergency Medicine, Emory-Children's Center for Developmental Lung Biology Emory University School of Medicine, Atlanta, GA, United States
dc.contributor.affiliation Kim, H.-Y., New England Research Institutes, Watertown MA, United States
dc.contributor.affiliation Wood, J., Children's Hospital of Los Angeles, Los Angeles, CA, United States
dc.contributor.affiliation Porter, J.B., University College London, London, United Kingdom
dc.contributor.affiliation Klings, E.S., The Pulmonary Center, Boston University School of Medicine, Boston, MA, United States
dc.contributor.affiliation Trachtenberg, F.L., New England Research Institutes, Watertown MA, United States
dc.contributor.affiliation Sweeters, N., Hematology-Oncology, Children's Hospital and Research Center Oakland, Oakland, CA, United States
dc.contributor.affiliation Olivieri, N.F., Toronto General Hospital, Toronto, ON, Canada
dc.contributor.affiliation Kwiatkowski, J.L., Children's Hospital of Philadelphia, Philadelphia, PA, United States
dc.contributor.affiliation Virzi, L., New England Research Institutes, Watertown MA, United States
dc.contributor.affiliation Singer, S.T., Hematology-Oncology, Children's Hospital and Research Center Oakland, Oakland, CA, United States
dc.contributor.affiliation Taher, A., American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Neufeld, E.J., Children's Hospital Boston, Boston, MA, United States
dc.contributor.affiliation Thompson, A.A., Hematology, Oncology and Stem Cell Transplant, Children's Memorial Hospital, Chicago, IL, United States
dc.contributor.affiliation Sachdev, V., Cardiovascular and Pulmonary Medicine Branch, National Heart Lung and Blood Institute, Bethesda, MD, United States
dc.contributor.affiliation Larkin, S., Children's Hospital Oakland Research Institute, Oakland, CA, United States
dc.contributor.affiliation Suh, J.H., Children's Hospital Oakland Research Institute, Oakland, CA, United States
dc.contributor.affiliation Kuypers, F.A., Children's Hospital Oakland Research Institute, Oakland, CA, United States
dc.contributor.affiliation Vichinsky, E.P., Hematology-Oncology, Children's Hospital and Research Center Oakland, Oakland, CA, United States
dc.contributor.authorAddress Morris, C. R.; Department of Pediatrics, Division of Emergency Medicine, Emory-Children's Center for Developmental Lung Biology Emory University School of Medicine, Atlanta, GA, United States; email:
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Internal Medicine;
dc.contributor.authorDepartment Internal Medicine
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials Morris, CR
dc.contributor.authorInitials Kim, HY
dc.contributor.authorInitials Wood, J
dc.contributor.authorInitials Porter, JB
dc.contributor.authorInitials Klings, ES
dc.contributor.authorInitials Trachtenberg, FL
dc.contributor.authorInitials Sweeters, N
dc.contributor.authorInitials Olivieri, NF
dc.contributor.authorInitials Kwiatkowski, JL
dc.contributor.authorInitials Virzi, L
dc.contributor.authorInitials Singer, ST
dc.contributor.authorInitials Taher, A
dc.contributor.authorInitials Neufeld, EJ
dc.contributor.authorInitials Thompson, AA
dc.contributor.authorInitials Sachdev, V
dc.contributor.authorInitials Larkin, S
dc.contributor.authorInitials Suh, JH
dc.contributor.authorInitials Kuypers, FA
dc.contributor.authorInitials Vichinsky, EP
dc.contributor.authorReprintAddress Morris, CR (reprint author), Emory Univ, Sch Med, Emory Childrens Ctr Dev Lung Biol, Dept Pediat,Div Emergency Med, Atlanta, GA 30322 USA.
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 5
dc.description.citedTotWOSCount 3
dc.description.citedWOSCount 3
dc.format.extentCount 9
dc.identifier.coden HAEMA
dc.identifier.pubmedID 23585527
dc.identifier.scopusID 84881369321
dc.publisher.address VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
dc.relation.ispartOfISOAbbr Haematologica
dc.relation.ispartOfIssue 9
dc.relation.ispartofPubTitle Haematologica
dc.relation.ispartofPubTitleAbbr Haematologica
dc.relation.ispartOfVolume 98
dc.source.ID WOS:000328542500017
dc.type.publication Journal
dc.subject.otherChemCAS arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3
dc.subject.otherChemCAS nitric oxide, 10102-43-9
dc.subject.otherChemCAS sildenafil, 139755-83-2
dc.subject.otherIndex arginine
dc.subject.otherIndex nitric oxide
dc.subject.otherIndex sildenafil
dc.subject.otherIndex adult
dc.subject.otherIndex article
dc.subject.otherIndex beta thalassemia
dc.subject.otherIndex blood flow velocity
dc.subject.otherIndex blurred vision
dc.subject.otherIndex clinical article
dc.subject.otherIndex dizziness
dc.subject.otherIndex Doppler echocardiography
dc.subject.otherIndex drug dose reduction
dc.subject.otherIndex drug efficacy
dc.subject.otherIndex drug safety
dc.subject.otherIndex drug tolerability
dc.subject.otherIndex dyspepsia
dc.subject.otherIndex dyspnea
dc.subject.otherIndex exercise
dc.subject.otherIndex eye disease
dc.subject.otherIndex fatigue
dc.subject.otherIndex female
dc.subject.otherIndex headache
dc.subject.otherIndex human
dc.subject.otherIndex international normalized ratio
dc.subject.otherIndex low back pain
dc.subject.otherIndex lung function
dc.subject.otherIndex male
dc.subject.otherIndex mortality
dc.subject.otherIndex open study
dc.subject.otherIndex peripheral edema
dc.subject.otherIndex phase 1 clinical trial
dc.subject.otherIndex phase 2 clinical trial
dc.subject.otherIndex phlebitis
dc.subject.otherIndex photophobia
dc.subject.otherIndex pilot study
dc.subject.otherIndex pulmonary hypertension
dc.subject.otherIndex sciatica
dc.subject.otherIndex side effect
dc.subject.otherIndex thalassemia
dc.subject.otherIndex walking
dc.subject.otherIndex Adult
dc.subject.otherIndex Echocardiography, Doppler
dc.subject.otherIndex Female
dc.subject.otherIndex Humans
dc.subject.otherIndex Hypertension, Pulmonary
dc.subject.otherIndex Male
dc.subject.otherIndex Middle Aged
dc.subject.otherIndex Pilot Projects
dc.subject.otherIndex Piperazines
dc.subject.otherIndex Purines
dc.subject.otherIndex Risk Factors
dc.subject.otherIndex Sulfones
dc.subject.otherIndex Thalassemia
dc.subject.otherIndex Vasodilator Agents
dc.subject.otherKeywordPlus SICKLE-CELL-DISEASE
dc.subject.otherKeywordPlus BETA-THALASSEMIA
dc.subject.otherKeywordPlus HEART-FAILURE
dc.subject.otherKeywordPlus NITRIC-OXIDE
dc.subject.otherKeywordPlus ARTERIAL-HYPERTENSION
dc.subject.otherKeywordPlus ARGININE BIOAVAILABILITY
dc.subject.otherKeywordPlus HYPERCOAGULABLE STATE
dc.subject.otherKeywordPlus PLATELET ACTIVATION
dc.subject.otherKeywordPlus ORAL SILDENAFIL
dc.subject.otherKeywordPlus TASK-FORCE
dc.subject.otherWOS Hematology

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