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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.
(427)| Volume 41, ISSUE 4, SUPPLEMENT , S188, April 2022

Persistent Iron Deficiency and Dysregulated Hepcidin Levels After LVAD Therapy

      Purpose

      Iron deficiency (FeD) is present in ∼50% of patients with heart failure (HF), and predicts worse exercise tolerance and outcomes. Hepcidin, an iron-regulating peptide hormone, inhibits iron absorption and bioavailability in states of excessive iron exposure, and is upregulated in pro-inflammatory conditions. High hepcidin levels correlated with refractoriness to oral iron repletion in HF patients with FeD. It is unknown if hepcidin levels are high after LVAD implant despite HF improvement.

      Methods

      Hepcidin ELISA assays were performed from biorepository plasma samples in consecutive LVAD patients within 2 weeks before LVAD implant and at 1, 3, and 6 months post-LVAD. FeD was defined as ferritin < 100 ng/mL, or ferritin = 100 - 299 ng/mL with transferrin saturation (Tsat) < 20%. P < 0.05 was considered significant comparison across all groups.

      Results

      Among 87 patients with a durable LVAD, median age was 62 years, 82% were male, and 56% had non-ischemic cardiomyopathy. By 6 months, 75 remained on LVAD (12 had transplant, explant or death). Median NT-proBNP decreased after LVAD (preop: 4348, 1mo: 2406, 3mo: 1802, 6mo: 1050 pg/mL, p=0.0001). Ferritin was highest at 1 month postop, but declined over time (p<0.0001) (Fig A). Despite use of intravenous/oral iron and blood transfusions in a subset of patients (Fig B), FeD was common (preop: 51%, 1mo: 42%, 3mo: 60%, 6mo: 66%). Change in hepcidin from preop to postop periods correlated with change in NT-proBNP (r = 0.2, p = 0.02). Hepcidin/Tsat ratios remained high at the level of refractoriness to oral iron seen in HF patients (Fig C).

      Conclusion

      Despite improvement in HF burden, LVAD patients were iron-deficient with high hepcidin/Tsat ratios that likely render them unable to maintain normal iron stores with dietary or oral iron supplements. Efforts to improve functional capacity and reduce reliance on blood transfusions in LVAD patients should include consideration of surveillance for FeD and correction with intravenous iron that circumvents hepcidin dysregulation.