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Systemic rapamycin to prevent in-stent stenosis in peripheral pulmonary arterial disease: early clinical experience

Published online by Cambridge University Press:  28 December 2015

Anna Hallbergson ,
Jesse J. Esch ,
Trang X. Tran ,
James E. Lock  and
Audrey C. Marshall
Anna Hallbergson
Affiliation:
Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America Children’s Heart Center, Skåne University Hospital, Lund, Sweden
Jesse J. Esch
Affiliation:
Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America
Trang X. Tran
Affiliation:
Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America
James E. Lock
Affiliation:
Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America
Audrey C. Marshall*
Affiliation:
Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America
*
Correspondence to: A. C. Marshall, MD, Department of Cardiology, Children’s Hospital of Boston, 300 Longwood Avenue, Boston, MA 02115, United States of America. Tel: +617 355 6529; Fax: +617 713 3808; E-mail: audrey.marshall@cardio.chboston.org
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Abstract

Objectives

We have taken a novel approach using oral rapamycin – sirolimus – as a medical adjunct to percutaneous therapy in patients with in-stent stenosis and high risk of right ventricular failure.

Background

Peripheral pulmonary artery stenosis can result in right ventricular hypertension, dysfunction, and death. Percutaneous pulmonary artery angioplasty and stent placement acutely relieve obstructions, but patients frequently require re-interventions due to re-stenosis. In patients with tetralogy of Fallot or arteriopathy, the problem of in-stent stenosis contributes to the rapidly recurrent disease.

Methods

Rapamycin was administered to 10 patients (1.5–18 years) with peripheral pulmonary stenosis and in-stent stenosis and either right ventricular hypertension, pulmonary blood flow maldistribution, or segmental pulmonary hypertension. Treatment was initiated around the time of catheterisation and continued for 1–3 months. Potential side-effects were monitored by clinical review and blood tests.

Results

Target serum rapamycin level (6–10 ng/ml) was accomplished in all patients; eight of the nine patients who returned for clinically indicated catheterisations demonstrated reduction in in-stent stenosis, and eight of the 10 patients experienced no significant side-effects. Among all, one patient developed diarrhoea requiring drug discontinuation, and one patient experienced gastrointestinal bleeding while on therapy that was likely due to an indwelling feeding tube and this patient tolerated rapamycin well following tube removal.

Conclusions

Our initial clinical experience supports that patients with peripheral pulmonary artery stenosis can be safely treated with rapamycin. Systemic rapamycin may provide a novel medical approach to reduce in-stent stenosis.

Keywords

In-stent stenosisrapamycintetralogy of Fallotperipheral pulmonary stenosisarteriopathy
Type
Original Articles
Information
Cardiology in the Young , Volume 26 , Issue 7 , October 2016 , pp. 1319 - 1326
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Copyright
© Cambridge University Press 2015 

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