Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia

Sadaf, Alina; Hasan, Babar; Das, Jai K; Colan, Steven D.; Alvi, Najveen

doi:10.1002/14651858.cd011626.pub2

Cited by 15 publications

(18 citation statements)

References 75 publications

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“…This finding is in accordance with the recent work by Eghbali et al, which indicated that myocardial T2* significantly changed after 1 year of treatment, from 21.9 ms to 24.5 ms 28. Another study conducted by Fernandes et al (2014) found an increase of 30% in the myocardial T2* after 1 year of treatment with amlodipine 27,37…”

Section: Discussionsupporting

confidence: 90%

“…This is explained by the mechanism of iron uptake in the heart tissues, which is mediated by the L-type calcium channels. The relative improvement of MIC in the amlodipine patients was consistent with a previous study by Fernandes et al (2016), also indicating a significant reduction in the MIC and improvement in the heart T2* after treatment with amlodipine in 57 patients older than 6 years of age 26,37…”

Section: Discussionsupporting

confidence: 90%

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<p>A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major</p>

Khaled¹,

Salem²,

Ezzat³

et al. 2019

DDDT

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Background Mortality rates increase due to iron deposition in the cardiac muscles of thalassemia major (TM) patients. Iron overload cardiomyopathy could be treated with a combination therapy of an iron chelator and an L-type calcium channel blocker. We designed a randomized controlled study to assess the potential of amlodipine, alongside chelation, in reducing myocardial iron concentration in TM patients compared with a placebo. Objectives This study aims to estimate the change in myocardial iron concentration (MIC) determined by magnetic resonance imaging after 6 months of treatment with amlodipine, as well as measuring the changes in the secondary outcomes (liver iron concentration (LIC), serum ferritin level (SF), and left ventricle ejection fraction (LVEF)) of study participants. Methods A single, randomized, placebo-controlled trial was performed in 40 β-Thalassemia major patients aged between 6 and 20 years old, who received either oral amlodipine 2.5–5 mg/day or a placebo, in addition to a Deferasirox chelation regimen in a 1:1 allocation ratio. Results After 6 months, a significant reduction was noted in the MIC of patients receiving amlodipine (n=20), compared with the patients receiving the placebo (n=20). At baseline, the mean was 0.76±0.11 mg/g dry weight, while at 6 months, the mean was 0.51±0.07 mg/g dry weight ( p <0.001). Also, there was a significant change in the myocardial T2* after 6 months; the amlodipine increased the myocardial T2* from 40.63±5.45 ms at baseline to 43.25±5.35 ms ( p <0.001). However, amlodipine did not significantly affect the secondary outcomes by the end of the study. Conclusion The addition of amlodipine to the standard chelation therapy in transfusion-dependent thalassemia major patients improves myocardial iron overload without increasing the adverse effects.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

<p>A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major</p>

Khaled¹,

Salem²,

Ezzat³

et al. 2019

DDDT

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“…These results were similar to those of a study by Sadaf et al. in which, although non‐significant changes in heart T2* were shown, other changes in MIC were significant, suggesting a possible role for baseline MIC in the response of thalassaemia patients to CCBs [30]. Although Fernandes et al.…”

Section: Discussionsupporting

confidence: 89%

“…Moreover, in the 2016 trial conducted by the same author, which employed a larger sample size, it was shown that a significant decrease in Myocardial Iron Concentration (MIC) after 12 months occurred only between the amlodipine and control groups whose baseline MIC was initially above the normal mean threshold (MIC > 0Á59 mg/g dry weight or T2* ≤ 35 ms) [10]. These results were similar to those of a study by Sadaf et al in which, although non-significant changes in heart T2* were shown, other changes in MIC were significant, suggesting a possible role for baseline MIC in the response of thalassaemia patients to CCBs [30]. Although Fernandes et al attributed the differences in cardiac T2* and MIC to the larger sample size in their 2016 study, we propose an additional hypothesis that needs to be confirmed with future studies.…”

Section: Discussionsupporting

confidence: 85%

Amlodipine as adjuvant therapy to current chelating agents for reducing iron overload in thalassaemia major: a systematic review, meta‐analysis and simulation of future studies

Elfaituri

Ghozy

Ebied³

et al. 2021

Vox Sanguinis

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Background and Objectives Iron overload in thalassaemia is a crucial prognostic factor and a major cause of death due to heart failure or arrhythmia. Therefore, previous research has recommended amlodipine as an auxiliary treatment to current chelating agents for reducing iron overload in thalassaemia patients. Materials and Methods A systematic review and meta‐analysis of the results of three randomized clinical trials evaluating the use of amlodipine in thalassaemia patients through 12 databases were carried out. Results Our final cohort included 130 patients. Insignificant difference in decreasing liver iron concentrations was found between amlodipine and control groups {weighted mean difference = −0·2, [95% confidence interval = (−0·55–0·15), P = 0·26]}. As regards serum ferritin, our analysis also showed no significant difference in serum ferritin between amlodipine and control groups {weighted mean difference [95% confidence interval = −0·16 (−0·51–0·19), P = 0·36]}. Similarly, there was insignificant difference in cardiac T2* between amlodipine and control groups {weighted mean difference [95% confidence interval = 0·34 (−0·01–0·69), P = 0·06]}. Conclusions Despite the growing evidence supporting the role of amlodipine in reducing iron overload in thalassaemia patients, our meta‐analysis did not find that evidence collectively significant. The results of our simulation suggest that when more data are available, a meta‐analysis with more randomized clinical trials could provide more conclusive insights.

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“…Despite incomplete characterization of iron-induced K + current alterations, amiodarone has been used to treat supraventricular arrhythmias commonly found in iron-overload patients ( Pennell et al, 2013 ). Potential role of LTCC blockers as an inhibitor of cardiac iron uptake is also being evaluated in clinical trials ( Fernandes et al, 2013 , 2016 ; Shakoor et al, 2014 ; Eghbali et al, 2017 ; Sadaf et al, 2018 ). It is still unknown whether the use of LTCC blockers will exert any significant electrophysiological effects.…”

Section: Forging the Field: Additional Issues To Be Explored In Iron-mentioning

confidence: 99%

Cellular Electrophysiology of Iron-Overloaded Cardiomyocytes

2018

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Iron, the most abundant transition metal element in the human body, plays an essential role in many physiological processes. However, without a physiologically active excretory pathway, iron is subject to strict homeostatic processes acting upon its absorption, storage, mobilization, and utilization. These intricate controls are perturbed in primary and secondary hemochromatoses, leading to a deposition of excess iron in multiple vital organs including the heart. Iron overload cardiomyopathy is the leading cause of mortality in patients with iron overload conditions. Apart from mechanical deterioration of the siderotic myocardium, arrhythmias reportedly contribute to a substantial portion of cardiac death associated with iron overload. Despite this significant impact, the cellular mechanisms of electrical disturbances in an iron-overloaded heart are still incompletely characterized. This review article focuses on cellular electrophysiological studies that directly investigate the effects of iron overload on the function of cardiac ion channels, including trans-sarcolemmal and sarcoplasmic reticulum Ca2+ fluxes, as well as cardiac action potential morphology. Our ultimate aim is to provide a comprehensive summary of the currently available information that will encourage and facilitate further mechanistic elucidation of iron-induced pathoelectrophysiological changes in the heart.

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Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia

Cited by 15 publications

References 75 publications

<p>A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major</p>

<p>A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major</p>

Amlodipine as adjuvant therapy to current chelating agents for reducing iron overload in thalassaemia major: a systematic review, meta‐analysis and simulation of future studies

Cellular Electrophysiology of Iron-Overloaded Cardiomyocytes

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