28 Mitral inflow at peak Valsalva and colour M mode propagation velocity will not be done. Congenital or acquired heart disease: Significant congenital defects will include cyanotic heart diseases, acyanotic heart diseases (atrial septal defect, ventricular septal defect, patent ductus arteriosus), with moderate-to-severe left to right shunt (as selleck compound determined by the treating paediatric cardiologist), and moderate-to-severe
valvular disease (mitral stenosis/mitral regurgitation, aortic stenosis/aortic regurgitation, tricuspid regurgitation/tricuspid stenosis, pulmonary stenosis/pulmonary regurgitation) whether congenital or acquired (other than thalassaemia). Heart failure: Defined as patients with known signs and symptoms of heart failure, such as worsening dyspnoea at rest or during exercise or exercise intolerance (NYHA functional II and above). Study design The use of amlodipine to treat hypertension has been established clinically. The role of this medication in retarding myocardial iron uptake
in increased iron states has been demonstrated in mice models. To date, only a single study has been published to assess the role of amlodipine as an iron uptake inhibitor.29 Our study will therefore be the largest study to date, and is a hybrid phase 2 and 3 randomised controlled trial. Utilising a prospective randomised controlled method, patients presenting to a single-center will undergo parallel group, simple randomisation with a 1:1 allocation. Sample size calculation To date, there is only a single human study that has been reported, and therefore limited information is available for sample size calculation. With the information gathered from Fernandes et al,29 using PASS 11 software, using a one-sided two-sample t test, we calculated
that group sample sizes of 23 in each arm (intervention and control) achieve 90% power to detect a difference of −6.6 between the null hypothesis that both group means are 21.7 and the alternative hypothesis that the mean of group 2 is 28.3 with known group SDs of 7.2 and GSK-3 8.0 and with a significance level (α) of 0.05000. However, the sample size for our current study is dictated by the grant budget. Our sample will therefore be 20 study participants. Given the 1:1 allocation ratio, 10 participants each will be randomised into either one of two groups; the control group (arm A) will comprise of standard chelation therapy alone while the intervention group (arm B) will receive amlodipine in addition to the standard chelation. Our future work and grant application will encompass larger studies to recruit more patients divided into different subgroups of chelation. Treatment arms Arm A: Receiving chelation therapy alone Arm B: Receiving chelation therapy plus amlodipine.