Attached as online supplementary appendix A, the protocol proves useful in helping to initiate appropriate chelation therapy particularly in the setting of severe myocardial iron overload. With the www.selleckchem.com/products/Paclitaxel(Taxol).html growing evidence that suggests L-TCCs as a possible pathway for ferrous ions (Fe2+) uptake into myocardial cells,13 we hypothesise that the use of L-type calcium channel blockers such as amlodipine will lead to a reduction in this myocardial iron deposition. Null hypothesis There is no difference between the efficacy of chelation plus amlodipine therapy and chelation therapy

alone in retarding the rate of myocardial iron deposition in patients with thalassaemia with iron overload and a constant transfusion need. Alternate hypothesis Chelation plus amlodipine therapy is more efficacious than chelation therapy alone in retarding the rate of myocardial iron deposition in patients with thalassaemia with iron overload and a constant transfusion need. Primary objective The aim of our study is to determine if amlodipine, an L-type specific calcium channel blocker, in addition

to the standard aggressive chelation therapy, can retard the deposition of iron in the myocardium of patients with thalassaemia with significant myocardial iron load with or without cardiomyopathy. Secondary objectives To determine if there is a difference in LV size, systolic and diastolic function in patients receiving amlodipine plus chelation therapy when compared with patients who receive only chelation therapy. Methods Operational definitions Myocardial iron load (see

online supplementary appendix B for study protocol): T2*: The myocardial T2* values in the mid-ventricular septum in the normal participants using a multiechocardiography acquisition is equal to are 33.3±7.8 ms.26 A shortening of myocardial T2* to <20 ms (implying increased myocardial iron) is associated with an increased chance of decreased LV function.27 Severity index based on T2*:25 Normal T2* >20 ms, Mild 15–20 ms, Moderate 10–15 ms, Severe <10 ms. Truncation model: Short T2* values Dacomitinib (4–10 ms) lead to a rapid decay in signal intensity with the signals of later echocardiography images buried in the background noise and motion. Therefore, in order to make the best-fit curve to an monoexponential curve, all data points less than 2 SNR (signal-to-noise ratio) will be removed. Liver Iron load: The values for T2* in normal participants for the liver with standard acquisition and multiechocardiography acquisition will be taken as 26.6±4.7 ms and 26.7±4.2 ms, respectively.26 LV systolic dysfunction: LV systolic dysfunction will be defined as following: EF z-score >−2: normal ≤−2 and >−3: mild ≤−3 and >−4: moderate ≤−4: severe.