These are not study visits. At all routine visits selleck chem Crenolanib to the outpatient haematology clinic. These are not study visits. At all monthly cardiology clinic visits that are part of the study. The start date, severity, treatment or action taken, stop date or determination of ongoing status, and assessment of causality will be noted for each event. SAEs will be documented when identified and relevant follow-up information recorded when available. Reporting AEs All SAEs will be reported to the sponsor within five working days of the SAE being identified even if the event is considered to be not related to the investigational product. SAEs will be reported to the Institutional Review Board (IRB)/Ethics Committee
(EC) per Aga Khan University’s Institutional policy. Copies of reports of all SAEs will be kept at the study site. A summary of AEs will be submitted to the sponsor and the IRB/ECs at least annually and to other entities (eg, safety monitoring board) if applicable. The anonymity of the participant shall be respected when forwarding all information. The participant’s name will not appear on any form or attachment. Managing AEs AEs that require symptomatic management only will be treated by the participant’s primary haematologist. AEs that require hospitalisation will also be managed by the participant’s primary haematologist and the costs incurred will be covered by the research fund. Cardiovascular AEs that require outpatient or inpatient management will
be treated by the PI and his cardiology team and all costs incurred will be covered by the research fund. Magnetic resonance and T2* imaging Myocardial T2* MRI is the most sensitive and easily reproducible index of myocardial iron deposition currently available.32 Myocardial iron deposition can be reproducibly quantified using T2*. This is the most significant variable for predicting a requirement for targeted treatment of myocardial iron overload
and it cannot be replaced by serum ferritin, liver iron or any other measurement. A shortening of myocardial T2* to <20 ms (implying increased myocardial iron) is associated with an increased chance of decreased LV function.27 For example, patients with T2* values >20 ms have a very low chance of decreased LVEF. T2* values of 10–20 ms indicate up to a 10% chance of decreased LVEF; 8–10 ms indicates an 18% chance; 6 ms indicates a 38% chance; and T2* Carfilzomib values of just 4 ms indicate a 70% chance of decreased LVEF.33 The following index will be used to categorise myocardial iron deposition severity based on T2* values:25 Normal: T2* ≥20 ms; Mild: T2* 15–20 ms; Moderate: T2* 10–15 ms; Severe: T2* <10 ms. Excellent T2* reproducibility between scanners produced by two different manufacturers supports the feasibility of widespread implementation of the technique.32 33 Thus, the inclusion of cardiac T2* assessment, in concert with conventional long-term assessments of tissue iron loading, is mandatory for the comprehensive evaluation of iron loading.