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Author Notes:

Author correspondence: Claudia R. Morris (claudia.r.morris@emory.edu)

This is publication number 29 of the Thalassemia Clinical Research Network (TCRN). TCRN member institutions and staff are listed in the Appendix.

The authors would like to thank the agencies which funded this study and the patients with thalassemia and their families who participated in this study.

Information on authorship, contributions, and financial & other disclosures was provided by the authors and is available with the online version of this article at www.haematologica.org.


Research Funding:

This work was supported by the NIH-NHLBI cooperative agreement U01 HL065238NIH grant.

This research was also supported in part by FDA grant 1R01FD003531-03 (to CRM), the Intramural Research Program of the NIH, NHLBI and by the following NIH-NHLBI cooperative agreements: U01-HL65232 and NIH/NCRR UL1-RR-024134 to the Children’s Hospital of Philadelphia, U01-HL72291 and by Harvard Catalyst CTSC U-01RR025758 to the Children’s Hospital, Boston, U01-HL65233 to the University Health Network Toronto General Hospital, UL1RR024131-01 to the Children’s Hospital & Research Center Oakland, U01-HL65244 and CTSC UL1-RR024996 to Weill Medical College of Cornell University, and U01-HL65238 to New England Research Institutes.

Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NHLBI.

Sildenafil Therapy In Thalassemia Patients With Doppler-Defined Risk Of Pulmonary Hypertension

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Journal Title:



Volume 98, Number 9


, Pages 1359-1367

Type of Work:

Article | Final Publisher PDF


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 13.3% (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.

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© Ferrata Storti Foundation

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