MRI for the diagnosis of cardiac and liver iron overload in patients with transfusion‐dependent thalassemia: An algorithm to guide clinical use when availability is limited

To the Editor: Iron overload (IOL) in the heart and liver is a common complication in transfusion-dependent thalassemia (TDT) and is associated with increased risk of morbidity and mortality. Owing to the different mechanisms of iron accumulation and the wide scope of disease severity, iron-loading rate varies between organs and, consequently, different organs are affected unevenly. Nowadays, several measurement methods are available to diagnose and quantify IOL in the various organs. Serum ferritin (SF) has been the standard IOL measure in patients with TDT, especially through serial assessment. Although inexpensive, practical, and commonly available, SF does not always predict body iron as it is an indirect indicator of tissue iron burden and is influenced by several factors such as infection and inflammation. Its correlation with liver iron concentration (LIC), specifically, is significant but varies with assessment method and disease, while its correlation with cardiac iron is poor. SF<1000 ng/mL has been associated with improved survival, while levels >2500 ng/mL indicate increased risk of cardiac morbidity and mortality. Alternatively, liver biopsy is a direct measure of iron in the liver; nevertheless, it is invasive and associated with risks and sampling and measurement errors. Direct tissue-iron measurement in the heart is not possible. Magnetic resonance imaging (MRI) has emerged as a non-invasive alternative for quantifying both liver (by R2 or T2* MRI) and heart (by cardiac T2* MRI) iron by overcoming shortcomings of SF measurement and liver biopsy. The technique is sensitive, validated, and internationally reproducible and enables better tailoring of iron-chelation therapy (ICT) by allowing identification of patients at risk of organ-specific morbidity and monitoring of ICT effectiveness in the liver and heart. Moreover, specific thresholds of LIC and cardiac T2* have been associated with clinical morbidities and mortality (LIC >7 mg/g dry weight associated with clinical morbidity; cardiac T2* <20 ms associated with arrhythmias, <10 ms associated with heart failure and death). Therefore, monitoring of liver and heart iron by MRI is considered a standard of care in thalassemia. Despite the established utility and widespread use of MRI, it is not always available or affordable, especially in resource-poor regions where TDT prevalence is highest. Moreover, in healthcare centers with large patient volumes, assessment for all patients at regular intervals is not always feasible because of financial constraints. Furthermore, although international guidelines recommend standard monitoring of liver and cardiac iron by MRI (every 6 months to 2 years, depending on several factors and IOL status), they do not provide sufficient guidance on when or whom to assess with MRI, especially when resources are limited and patient prioritization should be considered. To address the gaps in MRI utilization for TDT management in resource-poor settings, a panel of thalassemia experts from the Middle East, North Africa, and Asia Pacific regions met and proposed a simple and practical algorithm based on their experience of limitations and obstacles encountered with MRI utilization in those regions. The algorithm can guide the use of MRI for the detection and monitoring of IOL in TDT while considering its availability and accessibility for patients. Three scenarios were proposed based on availability and accessibility of MRI. Scenario 1: MRI available and accessible for all patients Age is the main determinant for initial MRI measurement. Consequently, in an ideal situation whereby MRI is easily accessible, all TDT patients aged 10 years, regardless of all other characteristics, would be candidates for baseline IOL screening by liver and heart MRI (based on validated methods and standard calibration). Of note, and in view of the recently published reports describing the early occurrence of liver and cardiac iron loading in children with TDT, MRI could still be requested in patients <10 years old informed by physician discretion, based on transfusion burden, SF levels, clinical complication profile, and MRI availability (Figure 1). Scenario 2: MRI available but not accessible for all patients Where MRI is not accessible for all patients, those aged 10–18 years with SF >2500 ng/mL should be prioritized, followed by any patient with SF >2500 ng/mL to optimize chelation therapy and prevent complications. In addition, patients with an increasing SF trend despite iron chelation should be considered for MRI screening as increasing SF levels could reflect an increase in organ iron loading. Liver and heart examination should be performed simultaneously when possible. The frequency of follow-up testing depends on the baseline reading: repeat MRI annually when cardiac T2* <20 ms or LIC >7 mg/g dry