Cardiac function during iron chelation therapy in adult non‐thalassaemic patients with transfusional iron overload

Abstract

It is well‐documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion‐dependent children suffering from ß‐thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT‐patients), iron chelation by desferrioxamine may affect the cardiac function in unknown ways, presumably because age‐related changes in the heart may cause iron chelation to affect the cardiac function in different ways. We therefore followed the left ventricular ejection fraction (LVEF) by multigated radionuclide angiography in 16 iron‐loaded ANT‐patients during iron chelation alone and after increasing the efficacy of chelation by vitamin C supplementation. During 12 months of iron chelation the mean LVEF fell significantly from 63.3% to 58.0% (p = 0.04). Individual changes in LVEF did not correlate significantly with age but with the pretreatment liver iron concentration. After initiation of vitamin C supplementation, the mean LVEF increased from 55.9% to 65.3% (p = 0.01). Our data suggest that in ANT‐patients prolonged desferrioxamine treatment without vitamin C supplementation may be associated with reduced LVEF, whereas vitamin C supplementation seems to benefit the cardiac function. Similar findings have not been described in ß‐thalassaemia and may hence be specific for ANT‐patients. However, our findings have to be confirmed by controlled studies.

Vitamin C May Improve Left Ventricular Ejection Fraction: A Meta-Analysis

“…Seven of them were parallel group trials and five were cross-over trials (Table 1). Three further trials were before-after trials: LVEF was first measured at baseline and then a second LVEF measurement was carried out following vitamin C administration of 1 month (49) or 6 months (38). The Basili et al trial was published in two reports (43,44) In the six cardiac trials, the mean age ranged from 56 to 69 years, and the baseline LVEF ranged from 35 to 62%.…”

d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats

“…), cirrhosis, and heart failure (Giardina and Grady 1995; Hershko et al 1998; for review, Murphy and Oudit 2010). Iron overload remains a serious complication for patients receiving blood cardioplegia (cardiopulmonary bypass procedures) (Pepper et al 1995) or multiple transfusions (anemia) as part of normal therapy (Jensen et al 1997; Mariotti et al 1998). Indeed, cardiac disease is the principle cause of death in transfused β-thalassaemia patients (Kremastinos et al 1995; Lombardo et al 1995).…”

“…Iron chelation therapy using deferoxamine (trihydroxamic acid, Desferal™ or DFO), has decreased the morbidity and mortality found in compliant transfused patients (Giardina and Grady 1995; Jensen et al 1997). However, concerns have emerged regarding its clinical use (Giardina and Grady 1995) as well as safety issues (Jensen et al 1997).…”

“…Iron chelation therapy using deferoxamine (trihydroxamic acid, Desferal™ or DFO), has decreased the morbidity and mortality found in compliant transfused patients (Giardina and Grady 1995; Jensen et al 1997). However, concerns have emerged regarding its clinical use (Giardina and Grady 1995) as well as safety issues (Jensen et al 1997). DFO is poorly absorbed from the gastrointestinal tract and must be administered parenterally; the discomfort during administration and other side effects contribute to noncompliance (Gujja et al 2010).…”

“…The combined use of DFO chelation with classic antioxidants (ascorbic acid, β-carotene, or vitamin E, with or without selenium) have shown promise as protective therapies (Giardina and Grady 1995; Whittaker et al 1996; Jensen et al 1997; Bartfay et al 1998; Hershko et al 1998). Furthermore, certain cardioactive agents also have antioxidant properties and may afford additional cardiovascular protection during chelation therapy of iron-overloaded individuals.…”