title: Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency.
abstract: In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling. Fifteen patients with iPAH and iron deficiency were included. Patients underwent a 6-minute walk test, cardiopulmonary exercise tests, cardiac magnetic resonance imaging, and a quadriceps muscle biopsy and completed a quality-of-life questionnaire before and 12 weeks after receiving a high dose of intravenous iron. The primary end point, 6-minute walk distance, was not significantly changed after 12 weeks (409 ± 110 m before vs. 428 ± 94 m after; P = 0.07). Secondary end points showed that intravenous iron administration was well tolerated and increased body iron stores in all patients. In addition, exercise endurance time (P < 0.001) and aerobic capacity (P < 0.001) increased significantly after iron therapy. This coincided with improved oxygen handling in quadriceps muscle cells, although cardiac function at rest and maximal [Formula: see text] were unchanged. Furthermore, iron treatment was associated with improved quality of life (P < 0.05). In conclusion, intravenous iron therapy in iron-deficient iPAH patients improves exercise endurance capacity. This could not be explained by improved RV function; however, increased quadriceps muscle oxygen handling may play a role. (
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT01288651).
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands ; Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Gerrina
authors.initials: G
authors.lastname: Ruiter
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands ; Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Emmy
authors.initials: E
authors.lastname: Manders
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands ; Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Happé
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands ; Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schalij
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Groepenhoff
authors.affiliation: National Pulmonary Hypertension Service, Hammersmith Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Luke S
authors.initials: LS
authors.lastname: Howard
authors.affiliation: National Institute for Health Research-Wellcome Trust Imperial Clinical Research Facility, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Wilkins
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: Bogaard
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van der Laarse
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.affiliation: Department of Pulmonology, Institute for Cardiovascular Research, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
keywords: exercise capacity; iron; right ventricle; skeletal muscle