Intravenous iron supplementation in pulmonary hypertension groups 1 to 4

Abstract

Background: Iron deficiency (ID) is common in patients with pulmonary arterial hypertension and has been associated with increased morbidity and mortality. We aimed to evaluate the therapeutic effects of iron supplementation in iron deficient patients with group 1 to 4 pulmonary hypertension (PH). Methods: A total of 85 PH patients (mean age 69.8 ± 12.0 years, 56.5% female) were included in this prospective trial. Patients were screened for ID at baseline. PH patients with ID received intravenous iron supplementation (500-1000 mg ferric carboxymaltose). PH patients without ID served as control group. At baseline and 16-week follow up, six-minute walk test (6MWT), laboratory testing and echocardiography were performed. Additionally, World Health Organization (WHO) functional class, fatigue score and quality of life (QoL) by the SF-36 questionnaire were assessed. Results: Overall, ID was present in 26.7% (n=8/30), 37.5% (n=9/24), 45.5% (n=10/22) and 44.4% (n=4/9) of patients in PH groups 1-4, respectively. In the total study population, iron restoration led to a significant mitigation of fatigue (p=0.01). However, 6MWT, WHO function class, NT-proBNP levels, QoL and right ventricular function did not change significantly. With regard to the underlying PH group, only PH group 3 patients experienced significant improvements in 6MWT distance (p=0.019), WHO functional class (p=0.017), fatigue (p=0.009) and some QoL domains, as compared to controls. Conclusions: ID was common in PH groups 1 to 4. Though intravenous iron supplementation adequately restored iron status and improved fatigue throughout all patients, in the underlying PH groups treatment was accompanied by improvements in exercise capacity, WHO function class and fatigue only in group 3 PH.

Keywords: Pulmonary hypertension; iron deficiency; iron supplementation.

Figure 1

Prevalence of iron deficiency (without anaemia) and iron deficiency anaemia in PH groups 1-4. Notes: Percentages refer to the cumulative percentages of the respective group. Abbreviations: CTEPH: chronic thromboembolic pulmonary hypertension. PAH: pulmonary arterial hypertension.

Figure 2

Changes in six-minute walk test distance (6MWT) from baseline to 16-week follow up in the intervention group (iron deficient PH patients) and controls, stratified by the underlying PH group 1-3. Notes: values represent mean ± standard deviation. P-values compare changes in controls and intervention group (Mann-Whitney U test). Asterisks indicate a significant p-value <0.05. Abbreviations: PH: pulmonary hypertension. 6MWT: six-minute walk test.

Figure 3

Changes in WHO function class from baseline to 16-week follow up in the intervention group (iron deficient PH patients) and controls, stratified by the underlying PH group 1-3. Notes: values represent mean ± standard deviation. P-values compare changes in controls and intervention group (Mann-Whitney U test). Asterisks indicate a significant p-value <0.05. Abbreviations: PH: pulmonary hypertension. WHO-FC: WHO function class.

Figure 4

Changes in nt-pro-BNP from baseline to 16-week follow up in the intervention group (iron deficient PH patients) and controls, stratified by the underlying PH group 1-3. Notes: values represent mean ± standard deviation. P-values compare changes in controls and intervention group (Mann-Whitney U test). Asterisks indicate a significant p-value <0.05. Abbreviations: NT-proBNP: N-terminal pro Brain Natriuretic Peptide. PH: pulmonary hypertension.

Figure 5

Changes in fatigue score from baseline to 16-week follow up in the intervention group (iron deficient PH patients) and controls, stratified by the underlying PH group 1-3. Notes: values represent mean ± standard deviation. P-values compare changes in controls and intervention group (Mann-Whitney U test). Asterisks indicate a significant p-value <0.05. Abbreviations: PH: pulmonary hypertension.

Figure 6

Changes in right ventricular function (TAPSE) from baseline to 16-week follow up in the intervention group (iron deficient PH patients) and controls, stratified by the underlying PH group 1-3. Notes: values represent mean ± standard deviation. P-values compare changes in controls and intervention group (Mann-Whitney U test). Asterisks indicate a significant p-value <0.05. Abbreviations: PH: pulmonary hypertension. TAPSE: tricuspid annular plane systolic excursion.