Evaluation of myocardial iron by magnetic resonance imaging during iron chelation therapy with deferrioxamine: indication of close relation between myocardial iron content and chelatable iron pool

Abstract

Evaluation of myocardial iron during iron chelation therapy is not feasible by repeated endomyocardial biopsies owing to the heterogeneity of iron distribution and the risk of complications. Recently, we described a noninvasive method based on magnetic resonance imaging. Here, the method was used for repeated estimation of the myocardial iron content during iron chelation with deferrioxamine in 14 adult nonthalassemic patients with transfusional iron overload. We investigated the repeatability of the method and the relationship between the myocardial iron estimates and iron status. The repeatability coefficient (2s D ) was 2.8 mol/g in the controls (day-to-day) and 4.0 mol/g in the patients (within-day). Myocardial iron estimates were elevated in 10 of all 14 patients at first examination, but normalized in 6 patients after 6 to 18 months of treatment. If liver iron declined below 350 mol/g all but one of the myocardial iron estimates were normal or nearly normal. At start (R 2 ‫؍‬ 0.69, P ‫؍‬ .0014) and still after 6 months of iron chelation (R 2 ‫؍‬ 0.76, P ‫؍‬ .001), the estimates were significantly and more closely related to the urinary iron excretion than to liver iron or serum ferritin levels. In conclusion, our preliminary data, which may only pertain to patients with acquired anemias, suggest the existence of a critical liver iron concentration, above which elevated myocardial iron is present, but its extent seems related to the size of the chelatable iron pool, as reflected by the urinary iron excretion. This further supports the concept of the labile iron pool as the compartment directly involved in transfusional iron toxicity. (Blood. 2003;101:4632-4639)

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

“…Note in this regard that 6 patients with serum ferritin levels >1000μg/L were not chelated because their physician did not consider the threshold for chelation achieved, and 7 because there had not been sufficient prior RBC transfusions. Lastly, there is evidence that, in some patients, effective long-term chelation (1-4 years) may stimulate haemopoiesis resulting in a return to transfusion independence [40] and decrease cardiac iron content [41]. This emphasizes the importance of applying generally accepted guidelines for iron chelation treatment while also considering individual patient factors beyond these guidelines to offer patients individualized treatment plans.…”

Management of the Thalassemias

“…Body iron burdens corresponding to hepatic iron concentrations exceeding 15 -20 mg iron/g liver, dw have been shown to place patients at heightened risk of cardiac disease and early death (Brittenham et al 1994;Telfer et al 2000), liver dysfunction (Jensen et al 2003), and acceleration of hepatic portal fibrosis (Angelucci et al 2002). Lack of certainty exists with respect to optimal hepatic iron concentrations that minimize the risk that hepatic fibrosis will progress to cirrhosis and its ultimate complication, hepatocellular carcinoma (Borgna-Pignatti et al 2004a,b;Ko et al 2007).…”

“…Therapy to maintain body iron at levels found in healthy, never-transfused individuals, corresponding to a hepatic iron of 0.2 -1.6 mg iron/g liver, dw (Brittenham et al 1982) may increase the probability of dose-related chelator toxicity. At the opposite extreme, body iron burdens corresponding to hepatic iron concentrations exceeding 15 -20 mg iron/g liver, dw place patients at risk of serious complications of iron loading (Brittenham et al 1994;Telfer et al 2000;Angelucci et al 2002;Jensen et al 2003). In transfusion-dependent patients with thalassemia, hepatic iron concentrations of 3-7 mg/g of liver, dw are generally regarded as optimal, seeming to minimize the risks both of adverse drug effects and complications from iron overload.…”

Non-Hfe Iron Overload: Is Phlebotomy the Answer?

“…Once a certain threshold of HIC is exceeded, Fe can begin to accumulate in the heart and other organs [14]. HICs above 130 mol/g dry weight are associated with increased risks of liver injury [15] whilst clinical cardiac toxicity occurs when HIC exceeds 270 mol/g [16].…”

“…HICs above 130 mol/g dry weight are associated with increased risks of liver injury [15] whilst clinical cardiac toxicity occurs when HIC exceeds 270 mol/g [16]. Changes in HIC generally precede changes in cardiac Fe loading [14], acting as an early warning of possible future cardiac complications.…”