title: Systemic rapamycin to prevent in-stent stenosis in peripheral pulmonary arterial disease: early clinical experience.
abstract: OBJECTIVE
  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.
authors.affiliation: 1Department of Cardiology,Boston Children's Hospital and Department of Pediatrics,Harvard Medical School,Boston,Massachusetts,United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Hallbergson
authors.affiliation: 1Department of Cardiology,Boston Children's Hospital and Department of Pediatrics,Harvard Medical School,Boston,Massachusetts,United States of America.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Esch
authors.affiliation: 1Department of Cardiology,Boston Children's Hospital and Department of Pediatrics,Harvard Medical School,Boston,Massachusetts,United States of America.
authors.forename: Trang X
authors.initials: TX
authors.lastname: Tran
authors.affiliation: 1Department of Cardiology,Boston Children's Hospital and Department of Pediatrics,Harvard Medical School,Boston,Massachusetts,United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Lock
authors.affiliation: 1Department of Cardiology,Boston Children's Hospital and Department of Pediatrics,Harvard Medical School,Boston,Massachusetts,United States of America.
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Marshall
mesh_terms: D000293:Adolescent; D000792:Angiography; D002648:Child; D002675:Child, Preschool; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary; D007223:Infant; D008297:Male; D056687:Off-Label Use; D011651:Pulmonary Artery / Q000601:surgery*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011666:Pulmonary Valve Stenosis / Q000628:therapy*; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D015607:Stents / Q000009:adverse effects*; D013771:Tetralogy of Fallot / Q000150:complications*
chemical_list: D020123:Sirolimus
keywords: In-stent stenosis; arteriopathy; peripheral pulmonary stenosis; rapamycin; tetralogy of Fallot