Burden of Cardiac Siderosis in a Thalassemia-Major Endemic Population: A Preliminary Report From Pakistan Najveen Alvi, MBBS,* Fateh A. Tipoo, MBBS, FCPS,w Ahmed Imran, BSc,z Muhammad N. Ashraf,y Asim Qidwai, MBBS,8 Mohammed Khursheed, MBBS, FRC.PATH, FRCP, FCPS,z Bushra Moiz, MBBS, FCPS,# Salman N. Adil, MBBS, FCPS,# Zehra Fadoo, MD,* Sadaf Altaf, MD,* Dudley J. Pennell, MRCP, MD, FESC, FACC, FRCP, FRFR, FAHA,** and Babar S. Hasan, MD* Objective: To describe the initial experience and demographics of T2* cardiac magnetic resonance–based myocardial-iron quantifi- cation of transfusion-dependent thalassemia-major (TM) patients from Pakistan and the correlation with serum ferritin. Methods: Eligible TM patients presenting between April 2014 and April 2015 to Aga Khan University Hospital, Pakistan, for T2*CMR were included. The severity of myocardial-iron deposi- tion was defined as follows: normal T2* > 20 ms, mild-moderate T2*10 to 20 ms, and severe T2* < 10 ms. Cardiac symptoms were classified using the NYHA functional classification. Echocardio- graphic systolic and diastolic functions were performed. Continuous variables were presented as the median (minimum- maximum value). Correlation was measured using the Spearman rank correlation. Multivariate logistic regression was used to determine factors associated with the NYHA functional class. Results: A total of 83 patients (49 male and 34 female) with TM, age 19 (5 to 45) years at presentation for T2*CMR, were reviewed. At presentation, 70% of the patients were classified as NYHA class II or worse. T2* < 20 ms was observed in 62.6% of the patients, with 47% showing severe iron deposition (T2 < 10 ms). No cor- relation of T2* < 20 ms (r = 0.157, P = 0.302) and T2* < 10 ms (r =  0.128, P = 0.464) was observed with serum ferritin. On multivariate analysis, lower T2* values correlated with a worsening NYHA functional class. Conclusions: There is a high prevalence of severe myocardial iron load in Pakistani TM patients. Serum ferritin did not correlate with T2* values. Lower T2* was the only clinical factor associated with the NYHA functional class. Key Words: thalassemia, cardiac T2* MRI, serum ferritin, iron chelation (J Pediatr Hematol Oncol 2016;38:378–383) M yocardial siderosis and its related complications remain the primary determinants of survival in chronically transfused thalassemia-major (TM) patients. A toxic cardiomyopathy, myocardial siderosis, is known to account for up to 70% of the morbidity and mortality, 1–3 with manifestations including complications such as arrhythmias, cardiomyopathy, pulmonary hypertension, and heart failure. 3–5 Resulting from a deposition of excess iron, these complications are reversible 6 provided timely assessment of the iron status and adequate management is initiated. This highlights the need for prompt accurate identification of the myocardial iron balance and its timely management. T2* cardiovascular magnetic resonance (T2* CMR) is a highly reproducible and sensitive technique that has been introduced for direct quantification of myocardial iron. 7 It is the only noninvasive modality that helps detect the clinically silent period of myocardial iron accumulation. The need for technical expertise and cost limits the uti- lization of this modality in developing countries. Therefore, in such settings, clinicians rely primarily on serum bio- markers, in particular serum ferritin, to ascertain the total iron load. Serum ferritin is, however, an indirect marker, representing only up to 1% of the total body iron. 8 Repeated serum ferritin measurements may help establish a trend 9 ; however, a nonlinear response at significantly high serum iron concentrations has been observed, 9 further limiting its use. Furthermore, it may be acutely influenced by spurious conditions including infections and inflamma- tion, 9 making it an unreliable measure of the cardiac iron load. Despite limitations, the ease of availability and cost- effectiveness account for a widespread use of this marker in endemic countries of the developing world. The major burden of thalassemia remains in develop- ing countries, with TM being endemic to many areas in the South-East Asia region. 10 The carrier rate of TM in Paki- stan alone is estimated at around 5% to 8%, with over 9000 children born every year with this disease. 11 This is in accordance with observations made by the World Health Organization that estimate the highest number of annual births with TM in the South-Asian region. 12 There is an extreme dearth of data, especially T2* CMR-acquired cardiac iron load assessment, from endemic regions and countries such as Pakistan. Ferritin-based assessment is still the mainstay of cardiac iron load evalu- ation in the region, but there is limited knowledge of its correlation with T2* CMR. In lieu of this, we present Received for publication September 16, 2015; accepted March 27, 2016. From the Departments of *Pediatrics and Child Health; wMedicine; zRadiology; yAga Khan University Hospital; zOncology, Section of Haematology and Oncology; #Pathology and Laboratory Medicine, Section of Haematology, Aga Khan University Hospital; 8Afzaal Memorial Thalassemia Foundation, Karachi, Pakistan; and **Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College, Lon- don, UK. N.A. and F.A.T. contributed equally. The authors declare no conflict of interest. Reprints: Babar S. Hasan, MD, Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan (e-mail: babar.hasan@aku.edu). Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved. ORIGINAL ARTICLE 378 | www.jpho-online.com J Pediatr Hematol Oncol  Volume 38, Number 5, July 2016 Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.