Intravenous Iron Therapy in Patients with Idiopathic Pulmonary Arterial Hypertension and Iron Deficiency

Ruiter, Gerrina; Manders, Emmy; Happé, Chris; Schalij, Ingrid; Groepenhoff, Herman; Howard, Luke; Wilkins, Martin R.; Bogaard, Harm Jan; Westerhof, Nico; Laarse, Willem J. van der; Man, Frances S. de; Vonk‐Noordegraaf, Anton

doi:10.1086/682217

Cited by 85 publications

(112 citation statements)

References 32 publications

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“…It has been suggested that iron deficiency is not just a marker of severity, but independently contributes to poor prognosis and exercise function [52]. No studies have assessed the impact of iron replacement on prognosis, but two open-label protocols have demonstrated improved aerobic capacity following intravenous iron, most probably due to improved skeletal muscle mitochondrial oxidative capacity [53,54]. Data were not reported on dyspnoea specifically, but improvements were seen in both studies in quality of life as assessed by the SF-36 score (36-item Short-Form Health Survey).…”

Section: Impact Of Comorbidities On Exercise Limitation/breathlessnesmentioning

confidence: 99%

Exertional dyspnoea in pulmonary arterial hypertension

et al. 2017

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Dyspnoea is a principal presenting symptom in pulmonary arterial hypertension (PAH), and often the most distressing. The pathophysiology of PAH is relatively well understood, with the primary abnormality of pulmonary vascular disease resulting in a combination of impaired cardiac output on exercise and abnormal gas exchange, both contributing to increased ventilatory drive. However, increased ventilatory drive is not the sole explanation for the complex neurophysiological and neuropsychological symptom of dyspnoea, with other significant contributions from skeletal muscle reflexes, respiratory muscle function, and psychological and emotional status. In this review, we explore the physiological aspects of dyspnoea in PAH, both in terms of the central cardiopulmonary abnormalities of PAH and the wider, systemic impact of PAH, and how these interact with common comorbidities. Finally, we discuss its relationship with disease severity.

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Section: Impact Of Comorbidities On Exercise Limitation/breathlessnesmentioning

confidence: 99%

Exertional dyspnoea in pulmonary arterial hypertension

et al. 2017

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“…Iron containing protein is also required for mitochondrial electron transport and catalyzes reactions that form NO[169]. Intravenous iron therapy in patients with idiopathic PAH was well tolerated and it improved endurance capacity; however, it did not alter cardiac function[170]. Thus, iron deficiency seems to be a more important prognosticator compared with anemia.…”

Section: Iron Homeostasis and Pahmentioning

confidence: 99%

Hematological disorders and pulmonary hypertension

Mathew

Huang

et al. 2016

WJC

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Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH.

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“…Recently, iron in PH patients has become an everincreasing focus for research with the general concept that iron deficiency is associated with disease phenotype [5,6]. In addition, intravenous iron therapy improves exercise endurance capacity in patients with idiopathic PH and iron deficiency [13]. However, it remains completely unknown whether PH leads to iron deficiency or iron deficiency enhances the development of PH.…”

Section: Discussionmentioning

confidence: 99%

Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice

et al. 2016

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Several recent observations provide the association of iron deficiency with pulmonary hypertension (PH) in human and animal studies. However, it remains completely unknown whether PH leads to iron deficiency or iron deficiency enhances the development of PH. In addition, it is obscure whether iron is associated with the development of pulmonary vascular remodeling in PH. In this study, we investigate the impacts of dietary iron restriction on the development of hypoxia-induced pulmonary vascular remodeling in mice. Eight- to ten-week-old male C57BL/6J mice were exposed to chronic hypoxia for 4 weeks. Mice exposed to hypoxia were randomly divided into two groups and were given a normal diet or an iron-restricted diet. Mice maintained in room air served as normoxic controls. Chronic hypoxia induced pulmonary vascular remodeling, while iron restriction led a modest attenuation of this change. In addition, chronic hypoxia exhibited increased RV systolic pressure, which was attenuated by iron restriction. Moreover, the increase in RV cardiomyocyte cross-sectional area and RV interstitial fibrosis was observed in mice exposed to chronic hypoxia. In contrast, iron restriction suppressed these changes. Consistent with these changes, RV weight to left ventricular + interventricular septum weight ratio was increased in mice exposed to chronic hypoxia, while this increment was inhibited by iron restriction. Taken together, these results suggest that iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice.

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Intravenous Iron Therapy in Patients with Idiopathic Pulmonary Arterial Hypertension and Iron Deficiency

Cited by 85 publications

References 32 publications

Exertional dyspnoea in pulmonary arterial hypertension

Exertional dyspnoea in pulmonary arterial hypertension

Hematological disorders and pulmonary hypertension

Iron is associated with the development of hypoxia-induced pulmonary vascular remodeling in mice

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