Introduction: PAH is a progressive disease with limited prognosis. Iron deficiency (ID) correlates in PAH patients with disease severity and mortality. Oral iron resorption is impaired by hepcidine in PAH. In a former pilot study, we could demonstrate a short-term benefit of i.v. iron substitution on exercise tolerance and quality of life. Subsequently, in this study we examined the effects of i.v. ferric carboxymaltose (FCM) in patients with PAH and ID for a period up to 15 months.
Hypothesis: We hypothesized that there are beneficial long-term effects in these patients on exercise tolerance and right heart function.
Methods: 64 patients with PAH and ID (serum iron < 10 μmol/L, ferritin <150 μg/L and transferrin saturation [TSAT] <15%), who were on a stable PAH therapy for ≥ 3 months, received FCM in a mean dosage of 914.1 ± 165.8 mg during the 15-month observation period. Twenty PAH patients without ID who did not receive FCM, served as matched controls. Follow-up included iron status, WHO functional class (WHO-FC), 6-minute walk distance (6MWD), echocardiography and NTproBNP levels.
Results: All patients in the intervention group obtained i.v. iron supplementation with FCM at baseline. 11 patients received a second FCM infusion, of which 2 patients needed a maximum of 3 FCM infusions due to re-occurence of ID. In patients with ID, FCM infusion resulted in an immediate and sustained improvement of iron status (serum iron, ferritin, TSAT, all p<0.05) during the course of our study. 2 months after the first FCM infusion, 6MWD improved from 354.9 ± 15.8 to 380.4 ± 14.7 m (p=0.016), which increased after 15 months to 389.6 ± 14.1 m. Also WHO-FC and NTproBNP levels improved. NTproBNP levels declined from 1423 ± 264 to 1062 ± 271 ng/L at 15 months. No significant changes were observed in the control group. After FCM administration no severe adverse events occured, only minimal side effects were observed.
Conclusions: Parenteral iron repletion with FCM was well tolerated in addition to targeted PAH therapy and led to beneficial long-term effects on excercice capacity, WHO-FC, NTproBNP serum levels, and risk stratification in PAH patients with ID. The results provide a promising basis for future, controlled studies on the long-term effect of supportive iron supplementation in PAH.
Source / Tilmann T Kramer, Thomas Viethen, Kristiana Natsina, Felix Gerhardt, Henrik Ten-Freyhaus, Daniel Dumitrescu, Martin Hellmich, Stephan Baldus and Stephan Rosenkranz
