Long‐term improvement in cardiac magnetic resonance in β‐thalassemia major patients treated with deferasirox extends to patients with abnormal baseline cardiac function

Abstract

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once‐daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a “real world” setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8‐11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2* <20 ms). A significant improvement in left‐ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF >56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX‐induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.

Cardiac T2* mapping: Techniques and clinical applications

“…Carpenter et al reported a worldwide survey of cardiac MR T 2 * that shows a moderate or severe cardiac iron overload condition at initial cardiac MR scanning 1 . To avoid this condition, early detection of iron loading by T 2 * measurement is needed and followed by an appropriate iron chelation therapy to improve the survival rate of hemochromatosis and transfusion‐dependent anemia patients 15,30,73,74 . Several studies reported a reduction of age recommendation to start the first T 2 * screening for thalassemia major patients from 10 years old to as early as 5 years old.…”

“…1 To avoid this condition, early detection of iron loading by T 2 * measurement is needed and followed by an appropriate iron chelation therapy to improve the survival rate of hemochromatosis and transfusion-dependent anemia patients. 15,30,73,74 Several studies reported a reduction of age recommendation to start the first T 2 * screening for thalassemia major patients from 10 years old to as early as 5 years old. The reduction promotes early detection of iron loading in pediatric patients.…”

“…89 Several chelating agents are used to excrete iron in the body, such as deferoxamine, deferasirox, and deferiprone, with a reportedly prescribed dose. 88 The pros and cons of monotherapy or combined therapy of the chelating agents were reported by recent studies, [4][5][6]8,73,74 promoting caution in chelation monitoring to control its side effects. Because of differences in chelation therapy practice between countries and regions, 2 monitoring of any complication effect of the therapy should be performed regularly according to a schedule proposed recently.…”

“…Iron overload monitoring is advisedly performed every 6 months when T 2 * values are below 10 msec. 9 Cardiac MR T 2 * measurement thus plays a vital role in updating the patient's iron status during the chelation therapy monitoring, 2,4,5,9,73,74 resulting in more accurate and effective iron chelation regimens for transfusiondependent anemia patients.…”

Keeping heart homeostasis in check through the balance of iron metabolism

“…The available treatment for this condition is iron chelation therapy, which has been shown to slow cardiac dysfunction and reduce mortality . As recent research shows, the beneficial effects of iron chelation extend even to patients with evident baseline cardiac dysfunction …”