Clinical utility of endocrine markers predicting myocardial siderosis in transfusion dependent thalassemia major.

BACKGROUND: Endocrinopathy due to iron overload is the most common morbidity whereas myocardial siderosis causing toxic cardiomyopathy is the leading cause of mortality among patients with transfusion dependent thalassemia major (TDTM). If detected early, this can be treated with aggressive chelation. T2* cardiac magnetic resonance imaging (CMR) guided chelation protocols are now the gold standard but have limited availability in low and middle-income countries. We hypothesized that markers of endocrine dysfunction would correlate with T2* CMR and can be used to predict the severity of myocardial siderosis and guide chelation therapy. METHODOLOGY: We undertook a multicenter retrospective study of 280 patients with TDTM to assess the prevalence of endocrinopathies and the predictive value of a number of individual and composite markers of endocrinopathy with T2* CMR. RESULTS: The prevalence of hypogonadism, stunting, hypoparathyroidism, and hypothyroidism was 82%, 69%, 40%, and 30%, respectively. The sensitivity of hypogonadism and stunting predicting severe myocardial siderosis was 90% and 80%, respectively. CONCLUSION: We conclude that clinical markers of endocrine dysfunction, especially hypogonadism (positive likelihood ratio [LR+] = 1.4, 95% confidence interval [CI] = 1.0-1.9; positive predictive value [PPV] = 77%, 95% CI = 70-82; negative predictive value [NPV] = 57%, 95% CI = 34-77] and stunting (LR+ = 1.3, 95% CI = 1.1-1.6; PPV = 64%, 95% CI = 60-69; NPV = 55%, 95% CI = 45-64) in TDTM can predict severe myocardial siderosis and can potentially guide chelation therapy, especially where access to T2* CMR is limited.

Establishment of a thalassaemia major quality improvement collaborative in Pakistan.

OBJECTIVES: The aim of this study was to establish multidisciplinary care for patients with transfusion-dependent thalassaemia (TDT) by creating a TDT quality improvement (QI) collaborative in a resource-constrained setting. This study presents our initial experience of creating this collaborative, the baseline characteristics of the participants, the proposed QI interventions and the outcome metrics of the collaborative. DESIGN AND SETTING: TDT QI collaborative is a database comprising patients with TDT from four centres in Karachi, Pakistan. Study variables included symptoms of cardiac or endocrine dysfunction, physical examination including anthropometry and Tanner staging, chelation therapy, results of echocardiography, T2* cardiac MRI (CMR) and serum ferritin. The main outcome of this collaborative was improvement in TDT-related morbidity and mortality. Interventions addressing the key drivers of outcome were designed and implemented. RESULTS: At the time of reporting, the total number of patients in this database was 295. Most patients reported cardiac symptoms corresponding to New York Heart Association class 2. Approximately half (52%, n=153) of the patients demonstrated severe myocardial iron overload (T2* <10 ms). Majority of the patients (58%, n=175) were not on adequate chelation therapy. There was no difference in echocardiographic measures of systolic and diastolic left ventricle among the different spectrums of iron overloaded myocardium. CONCLUSION: Using T2* CMR and endocrine testing, we have identified significant burden of iron siderosis in our patients with TDT. Lack of adequate iron load assessment and standardised management was observed. Interventions designed to target these key drivers of outcome are the unique part of this QI-based TDT registry.