Pediatric Hematology Oncology Journal 3 (2018) 64e69

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Pediatric Hematology Oncology Journal

journal homepage: https://www.elsevier.com/journals/pediatric-
hematology-oncology-journal/

Decreasing cardiac iron overload with Amlodipine and Spirulina in

children with b-thalassemia
Sahar M. El-Haggar a, **, Mohamed R. El-Shanshory b, Rasha A. El-shafey c,
Mohamed S. Dabour a, *
a
Clinical Pharmacy Department, Faculty of Pharmacy, Tanta University, Egypt
b
Pediatrics Department, Faculty of Medicine, Tanta University, Egypt
c
MR Unit, Radiology and Imaging Department, Tanta University Hospital, Faculty of Medicine, Tanta University, Egypt

a r t i c l e i n f o a b s t r a c t

Article history: Background & aim: Iron overload in thalassemia major (TM) leads to excessive iron deposition in a wide
Received 15 May 2018 variety of tissues especially the heart leading to iron-overload cardiomyopathy, which is the major
Received in revised form determinant of survival in those patients. Our goal was to study effects of Amlodipine and Spirulina on
12 August 2018
iron loading when added to chelation therapy in patients with TM.
Accepted 4 October 2018
Available online 11 October 2018
Method: Forty patients with TM undergoing chelation therapy were randomized into two groups (1:1);
group 1 received Amlodipine 5 mg/day, and group 2 received Spirulina 250 mg/kg/day for 3 months.
Patients were assessed for MRI examination (cardiac T2*) and laboratory data including ferritin, troponin
Keywords:
Amlodipine
I, and NT-proBNP levels at baseline and after 3 months.
Spirulina Results: After 3 months, cardiac T2* increased significantly from 21.8 ± 7.7 ms to 22.94 ± 7.1 ms (p ¼ 0.03)
Cardiac iron overload in Spirulina group, and from 21.9 ± 8.7 ms to 24.6 ± 9.4 ms (p ¼ 0.007) in Amlodipine group. There was
b-thalassemia significant reduction in ferritin levels in Spirulina group (p ¼ 0.007), but not in Amlodipine group
MRI (p ¼ 0.09). In addition, NT-proBNP level decreased significantly in both groups. There was no statistically
NT-proBNP significant difference between both groups concerning cardiac T2*, serum ferritin, troponin I, and NT-
proBNP levels at 3 months.
Conclusion: Our findings suggest that the use of Amlodipine or Spirulina as a complementary treatment
with standard chelation therapy could reduce iron overload in patients with TM.
This trial was registered at www.ClinicalTrials.gov as #NCT02671695.
© 2018 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics. Publishing Services by
Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).

1. Introduction
Beta thalassaemia is a common inherited blood disorder that
results from genetic mutations with severe reduction or absent
production of the b-globin chain of the hemoglobin tetramer. This
results in ineffective erythropoiesis caused by an excess of a-globin
chains and severe anemia that is life-threatening from z1 to 2
years of age [1,2]. Beta thalassaemia is associated with severe he-
molytic anemia that requires frequent lifelong blood transfusions,
* Corresponding author.
** Corresponding author.
E-mail addresses: dabourmo91@gmail.com, mohamed.dabour@pharm.tanta.
edu.eg (M.S. Dabour).
Peer review under responsibility of Pediatric Hematology Oncology Chapter of
Indian Academy of Pediatrics.
often on a monthly or bi-monthly basis [3], however, the iron load
of z200 mg per unit combined with mildly elevated gastrointes-
tinal iron uptake resulting from hepcidin suppression [4] increases
total body iron, leading to a requirement for lifelong therapy with
iron chelation to prevent or reverse iron-related complications
[1,5].
Iron overload leads to excessive iron deposition in a wide variety
of tissues, including the heart, the liver, and endocrine glands
[6e8]. Cardiac complications are the most important, being
responsible for more than half of the deaths in this population
deeming it the major survival determinant in thalassemic patients
[9]. Therefore, the heart is the target fatal organ in thalassemia.
Once heart failure develops, the prognosis is usually poor [10e12].
Iron burden in the heart can be reduced by chelation therapy,
however, its toxicity and expense limit its application and wide-
spread use in developing and undeveloped countries, where the

https://doi.org/10.1016/j.phoj.2018.10.001
2468-1245/© 2018 Pediatric Hematology Oncology Chapter of Indian Academy of Pediatrics. Publishing Services by Elsevier B.V. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 S.M. El-Haggar et al. / Pediatric Hematology Oncology Journal 3 (2018) 64e69
global burden from iron overload is particularly high [11,13,14].
Therefore, several studies are frequently presented for the devel-
opment of new treatment strategies for increasing survival and
improving quality of life for iron-overload patients.
Previous in vitro studies demonstrated that one of the major
pathways for iron to enter into cardiomyocytes are the L-type cal-
cium channels and, in mice, calcium channel blockers lessened the
myocardial iron overload [6,11]. Being an inexpensive, broadly
available calcium-channel blocker (CCB) with a well-known safety
profile in both adults and children [15], Amlodipine was considered
in a recent trend by several clinical trials [13].
Spirulina is a multicellular filamentous cyanobacterium
(blueegreen alga) with a long history of use as a well-recognized
food supplement for humans and animals [16]. Spirulina is a rich
source of proteins and vitamins, especially vitamin B12, minerals,
essential fatty acids, carotenoids and phycocyanins [17]. Although
Spirulina is used in many countries as a nutritional supplement,
recently more attention has been paid to its therapeutic potential.
Spirulina has shown hypolipidemic [18], hypoglycemic [19], anti-
hypertensive [20,21] anti-viral [22], liver-protecting, anti-cancer,
anti-inflammatory and antioxidant properties [23]; as well as
positive effects on immunity( [17,24,25]. Moreover, Spirulina is not
expensive, has no side effects and is not toxic in nature [17] which
promotes investigators to conduct clinical trials to test the safety
and efficacy of this supplement in thalassemic patients. The car-
dioprotective effect of Spirulina may be attributed to its antioxidant
and iron chelating effects that can produce up regulation of anti-
oxidant enzymes, provocation of a free radical scavenging enzyme
system and excretion of iron from the body by effective chelation.
Several in vitro studies have identified the iron chelating ability of
Spirulina or its extracts [26,27].
The cardiomyopathy may be reversible if iron chelation treat-
ment is intensified in time, but the diagnosis is often delayed by the
unpredictability of cardiac iron deposition and the late develop-
ment of symptoms and echocardiographic abnormalities [28].
Cardiac MR (CMR) is considered the gold standard investigation for
early detection of cardiac iron overload and can reliably identify
patients with subclinical cardiac iron concentrations and stratify
their risk of subsequent cardiac dysfunction [29,30].
The use of clinical magnetic resonance imaging (MRI) to assess
the extent of iron loading in organs has revolutionized the diag-
nosis, management and treatment of beta thalassaemia patients
[31]. MRI has two significant advantages over the other imaging or
invasive diagnostic techniques, namely; accurate measurement of
both cardiac structure and function; and direct quantification of
iron loading due to minimization of magnetic relaxation times T1,
T2 and T2* in the presence of iron. These properties make it the
ideal tool for clinical monitoring of beta thalassaemia patients
providing noninvasive monitoring of cardiac iron deposition and
the resulting iron induced cardiomyopathy [32e34].
In the present study, we investigated the use of the calcium
channel blocker Amlodipine and Spirulina as novel and comple-
mentary treatment to standard chelation therapy in reducing iron
overload in patients with TM using MRI.
2. Patients and methods
2.1. Patients
Our study was conducted from February 2015 to January 2017.
This study was carried out at the Hematology Unit of Tanta Uni-
versity Hospital. Forty patients were included in the study based on
the criteria of at least 8 years of age (for compliance with the MR
examination), regular transfusions, and iron overload with no
perspective of changing the chelation therapy in the following 3
65
months. Exclusion criteria were patients with significant left ven-
tricular dysfunction (ejection fraction < 35%), advanced atrioven-
tricular conduction disturbances, other types of hemolytic anemias,
and formal contraindications to MR examinations (such as
implantable cardiac device).
To minimize an impact from changes in chelation during the
study, only those patients were chosen who had a track record of
good compliance, and it was not planned to alter their current
chelation regimen in the short run.
2.2. Study design
A total number of 40 patients who fulfilled the selection criteria
were enrolled in the study. The study has been approved by the
National Research Ethics Committee (Tanta University Ethical
Committee) and has been performed in accordance with the ethical
standards as laid down in the 1964 declaration of Helsinki and its
later amendments or comparable ethical standards. All patients’
legal guardians provided written informed consent before enroll-
ment in the study. The study is registered at www. ClinicalTrials.gov
as NCT02671695.
The study design was comparative randomized clinical trial to
study and compare the effect of two different medications (Amlo-
dipine and Spirulina). Forty patients with TM undergoing chelation
therapy were randomized into two groups (n ¼ 20) as follows:
group 1 received Amlodipine 5 mg/day, and group 2 received
Spirulina 250 mg/kg/day with a maximum dose of 4 gm for 3
months. Patients were followed up periodically for assessment of
compliance to the study medication and adverse events. All blood
samples were obtained just before blood transfusion. Blood sam-
ples were collected in serum tubes and centrifuged. Then, serum
was separated, coded, and stored at 80  C until analysis.
At baseline, patients were assessed for clinical characteristics,
MRI examination (cardiac T2*) as well as biochemical data
including ferritin, troponin I (cTnI), N-terminal pro-B-type natri-
uretic peptide (NT-proBNP) levels. All patients repeated laboratory
and MR evaluation at 3 months. Patients were followed up every
blood transfusion visit for assessment of compliance to the study
medication and adverse events.
2.3. MRI examination
Magnetic resonance imaging examinations were performed for
all patients in MR unit, Radiology and Imaging Department, Tanta
University Hospital. Iron in the myocardium was quantified by
measuring T2* (1/R2*), a MR relaxation parameter that has been
shown to vary inversely with tissue iron concentration [35,36].This
technique has high reproducibility and inter-MRI scanner agree-
ment [35,37,38].
MRI measurements were performed using a 1.5-Tesla Clinical
MRI Scanner (Toshiba, GE medical system). Myocardial T2* was
assessed from single short-axis mid-left ventricular slice using a
cardiac-gated, segmented, multiecho gradient echo sequence at
twelve echo times TE (1.7/2.2/3/3.5/4/5/5.5/8/9/10/12/15) with a
repetition time (TR) of 20 ms, Flip angle ¼ 20, Field of view
(FOV) ¼ 40  38 mm, Matrix (frequency x phase) ¼ 128 x 192
pixels, Slice thickness ¼ 10 mm with no gap interval.
Signal intensity was obtained using an ROI (Region of Interest)
drawn through the full thickness of the septum wall of the
myocardial short axis image. The ROI was chosen to include both
endocardium and epicardium layers of the heart and to include
septum from both ventricular intersections as shown in Fig. 1.
Signal intensities were obtained with the original unit’s software
(Toshiba, GE medical system). The values of both signal intensity
and TEs manually were entered into an Excel spreadsheet. The
66 S.M. El-Haggar et al. / Pediatric Hematology Oncology Journal 3 (2018) 64e69
Fig. 1. T2* quantification. Signal intensity was obtained using an ROI (Region of In-
terest) drawn through the full thickness of the septum wall of the myocardial short
axis image.
mean signal intensity in each slice with varying TEs was used to fit
the exponential signal decay curve using the formula SI¼ SI0 eeTE/
T2*
in the spreadsheet where SI is the signal intensity and TE is the
echo time as shown in Fig. 2.
Patients were classified as having normal heart iron concen-
trations (T2*>20 ms), mild (T2* ¼ 15e20 ms), moderate
(T2* ¼ 10e15 ms) or severe concentrations (T2*< 10 ms) according
to previously published guidelines [39e41].
2.4. Biochemical assays
Serum ferritin, cardiac troponin I (cTnI), NT-proBNP levels were
assayed by Enzyme-Linked Immunosorbent Assay (ELISA) using
commercial kits. Assay was carried out according to the manufac-
turers’ instructions for assay of serum ferritin (Immunospec, USA),
cTnI (Biocheck, USA), NT-proBNP (cloud-clone, USA).
2.5. Statistical analysis
Data were analyzed using SPSS statistical package version 22.0,
IBM Corporation Software Group, USA. Paired Student’s t-test was
used to assess any significant difference between each group at
baseline and after 3 months of treatment course. unpaired Stu-
dent’s t-test was used to assess any significant difference among
the two groups at baseline and after 3 months. Values were pre-
sented as mean ± standard deviation (SD). Pearson’s correlation
Fig. 2. Data analysis using excel spread sheet. The signal intensity (TE) is plotted
against multiple TE values (1.7/2.2/3/3.5/4/5/5.5/8/9/10/12/15 ms). The exponential
signal decay curve is then constructed. T2* value is calculated automatically by the
preset formula, and here it is 13.5 ms which is considered moderate; equivalent to
myocardial iron concentration (MIC) 1.88 mg/g.
test was used to assess the correlation between measured param-
eters after the effective intervention. All p values were two-tailed
and p < 0.05 was considered significant for statistical analysis.
3. Results
Baseline characteristics of patients are shown in Table 1. No
significant differences were found among the participants,
including the type of chelation therapy. No serious adverse events
related to Spirulina and Amlodipine were detected. No significant
reductions in systemic blood pressure were observed and no sig-
nificant changes in chelation therapy were made during the trial in
both groups (type of medication or dosing). Summary of the
mean ± SD values of variables at baseline and after 3 months in
both groups is presented in Table 2.
After 3 months, cardiac T2* increased significantly from
21.8 ± 7.7 ms to 22.94 ± 7.1 ms (p ¼ 0.03) in Spirulina group, and
from 21.9 ± 8.7 ms to 24.6 ± 9.4 ms (p ¼ 0.007) in Amlodipine
group.
Compared with baseline, ferritin level decreased significantly in
Spirulina group from 4089.8 ± 1029.9 ng/ml to 3696.2 ± 1044.7 ng/
ml (p ¼ 0.007), While there was no significant reduction in ferritin
level in Amlodipine group (p ¼ 0.09).
Both groups showed significant reduction in NT-proBNP level
after 3 months. In Spirulina group, NT-proBNP level decreased
significantly from 167.2 ± 61.7 pg/ml to 151.2 ± 53.7 pg/ml
(p ¼ 0.017). In Amlodipine group, NT-proBNP level decreased
significantly from 156.1 ± 60.2 pg/ml to 131.2 ± 47.1 pg/ml
(p ¼ 0.0009).
Troponin I did not change significantly in both groups along the
3 months of follow-up from baseline. Although Amlodipine
increased T2* more than Spirulina, there was no statistically sig-
nificant difference between both groups concerning cardiac T2* at 3
months.
When comparing the two groups after treatment, there was no
significant difference between both groups concerning cardiac T2*,
serum ferritin, troponin I, and NT-proBNP levels. Additionally, there
was no significant correlation in both groups between the change
in cardiac T2* at 3 months and changes in ferritin, NT-proBNP, or
Troponin I.
4. Discussion
Iron-overload cardiomyopathy, resulting from TM, is respon-
sible for considerable cardiovascular morbidity and mortality on a
global scale [42e46]. Myocardial injury is the major determinant of
survival in patients with TM [9,33,47]. The treatment options of
myocardial iron overload are currently restricted to a definite
number of chelation strategies, with several constraints arising
from the necessity of elevated doses, and concomitant side effects
[48].
The present study evaluates whether Amlodipine and Spirulina
could have effect on myocardial iron overload in TM patients. Our
findings suggest that both Amlodipine or Spirulina reduce
myocardial iron overload when added to standard iron chelation in
TM patients and may represent a novel and complementary
treatment for iron overload in patients with thalassemia major.
In the present study, there was significant decrease in serum
ferritin in patients after Spirulina therapy. Such a reduction was not
observed in Amlodipine group. Our results are in accordance with
other studies which found that Amlodipine has no effect on serum
ferritin [49,50]. This finding was also in consistent with another
study which found a significant decrease in serum ferritin levels in
patients with TM after Spirulina treatment [51].
This finding is compatible with the mechanisms by which the
 S.M. El-Haggar et al. / Pediatric Hematology Oncology Journal 3 (2018) 64e69 67

Table 1
Baseline characteristics of patients.

Variable Spirulina group (N ¼ 20) Amlodipine group (N ¼ 20) P value

Age, y (range) 10.7 ± 2.3 (8e15) 10.1 ± 1.4 (9e15) 0.3253

Sex m: f 10:10 12:8
Female (%) 10 (50) 8 (40) 0.75
Weight (kg) 30.4 ± 10.26 28.1 ± 9.65 0.4699
Height (cm) 113.2 ± 17.38 110.4 ± 18 0.6197
Splenectomy (%) 16 (80) 13 (65) 0.48
Hepatitis C (%) 18 (90) 16 (80) 0.66
Chelation therapy
Deferasirox 13 (65) 15 (75)
Deferoxamine 7 (35) 5 (25) 0.73
Baseline serum ferritin (ng/ml) 4089.8 ± 1029.9 4067.1 ± 733.2 0.9191
Cardiac T2* (ms) 21.8 ± 7.7 21.9 ± 8.7 0.971

Data presented as mean ± SD.

Table 2
Patients’ variables at baseline and 3 months after treatment.

Variable Spirulina group (n ¼ 20) Amlodipine group (n ¼ 20) p**

Baseline 3 months p* Baseline 3 months p*

ferritin (ng/ml) 4089.8 ± 1029.9 3696.2 ± 1044.7 0.0072 4067.1 ± 733.2 3917.7 ± 768.1 0.096 0.436
Troponin I (ng/ml) 0.152 ± 0.059 0.149 ± 0.055 0.585 0.149 ± 0.048 0.141 ± 0.048 0.328 0.592
NT-proBNP (pg/ml) 167.2 ± 61.7 151.2 ± 53.7 0.0173 156.1 ± 60.2 131.2 ± 47.1 0.0009 0.216
Cardiac T2* (ms) 21.8 ± 7.7 22.94 ± 7.1 0.0383 21.9 ± 8.7 24.6 ± 9.4 0.0071 0.527

Data presented as mean ± SD, * p-value for the intragroup comparison (baseline vs 3 months), by paired sample t-test. ** p-value for the intergroup comparison (comparison of
posttreatment values between Spirulina and Amlodipine), by unpaired sample t-test.

Amlodipine blocks iron uptake [11]. Most of serum ferritin-bound
iron does not depend on active uptake by voltage-gated channels,
so blocking calcium channels by Amlodipine was not expected to
affect ferritin-bound iron kinetics. On the contrary, ferritin
reducing effect in Spirulina group could be explained by the iron
chelating ability of Spirulina. A number of in vitro studies have
identified the iron chelating ability of Spirulina or its extracts. These
studies were able to identify and purify iron-chelating peptides
from Spirulina protein hydrolysates [27], confirmed the iron-
binding properties of Spirulina extract and phycocyanin(26), and
observed that Spirulina showed iron-chelating activities in dose-
dependent manner [52].
In our study, Amlodipine showed a 13.4% reduction in Myocar-
dial Iron Concentration (MIC) and a 12.4% increase in T2* which
represent a decrease of 0.14 mg/g in myocardial iron in 3 months
and confirms the findings from a previous one-year human pilot
trial that showed 30% increase in heart T2* [53]. This pilot trial was
further confirmed by a larger multicenter, randomized, placebo-
controlled, and double-blind trial, in which, Amlodipine resulted
in 21% reduction in MIC in thalassemic patients randomized to
Amlodipine plus standard iron chelation therapy in 1 year(49).
Moreover, patients treated with Amlodipine showed significant
decrease in MIC at 12 months compared with patients treated with
placebo after 12 months of treatment (P ¼ 0.02) [49]. Additionally,
there are 2 current phase II/III trials (clinicaltrials.gov;
NCT02065492) (Karachi, Pakistan), and NCT02474420 (Toronto,
Canada) testing the therapeutic effects of Amlodipine in addition to
standard therapy in patients with secondary iron overload. Our
result is also in line with the experimental data that demonstrated
that voltage-gated calcium-channel blockers like Amlodipine and
verapamil reduced 45% of the iron uptake in mouse myocardial
cells and reduced oxidative stress while protecting diastolic and
systolic cardiac function [6].
The obtained results from our study showed significant increase
of 5% in cardiac T2* after Spirulina therapy compared to pretreat-
ment. The decrease in serum ferritin due to iron chelating activity
of Spirulina, besides the antioxidant activity could explain subse-
quent decrease in cardiac iron and increase in cardiac T2*. Our
study is the first clinical trial to address the potential effect of
Spirulina supplementation on cardiac iron overload using CMR in
multi transfused children with TM. The antioxidant properties of
Spirulina play an important role to protect the heart of thalassemic
patients from iron overload due to the pivotal role of oxidative
stress in iron-overload cardiomyopathy [6]. Several preclinical and
clinical studies revealed the cardioprotective effect of Spirulina by
its anti-oxidant activity. One of these studies demonstrated that
both the liver and heart of rats may be protected by Spirulina
against oxidative stress by two mechanisms; minimizing the ac-
tivity of nicotinamide adenine dinucleotide phosphate oxidase and
scanting the activity of superoxide dismutase and glutathione
peroxidase [54]. Moreover, numerous in vivo studies have proved
the potential of Spirulina to combat oxidative stress induced by
heavy metals (such as mercury, lead, iron, and chromium) which
induces reactive oxygen species and an associated oxidative stress
response [55e59]).
In our work, both Spirulina and Amlodipine have no significant
effect on troponin I levels. Concerning normal levels of cTnI in our
patients, this finding was in agreement with another study which
showed that the mean of serum cTnI in the thalassemia group was
higher than in the control heathy group but statistically not sig-
nificant (p ¼ 0.82) [60]. However, several studies found that
troponin I levels were higher in thalassemia major patients
compared to healthy volunteers [61e63].
Additionally, the present study investigated the effect of
Amlodipine and Spirulina on concentrations of cardiac troponin I
(cTnI), as a quantitative marker of cardiomyocyte injury, and NT-
proBNP, as a quantitative marker of hemodynamic cardiac stress.
NT-proBNP is produced by cardiac tissue in response to volume
overload and ventricular wall distension and may be elevated after
myocardial ischemia, hypoxia, and fibrosis [64]. In our study, both
Amlodipine and Spirulina decreased NT-proBNP levels. Amlodipine
as a vasodilator significantly decreased the levels of NT-proBNP
68 S.M. El-Haggar et al. / Pediatric Hematology Oncology Journal 3 (2018) 64e69
(p ¼ 0.0009) which predicts heart failure and other cardiovascular
disease events. This result was in agreement with several studies
which proved that Amlodipine reduced NT-proBNP levels by 36.5%
at 6 months in the Anglo-Scandinavian Cardiac Outcomes Trial
(ASCOT) [65], and in patients with COPD-induced pulmonary hy-
pertension after two weeks of treatment [66].
This is the first study to examine the effect of Spirulina on NT-
proBNP level. However, this effect could be explained by the ef-
fect of Spirulina on vascular reactivity illustrated by multiple
studies which noted that Spirulina induces a tone-related increase
in both the synthesis and release of: nitric oxide by the endothe-
lium and a vasodilating cyclooxygenase-dependent metabolite of
arachidonic acid. On the other hand it was also found to cause a
decrease in the synthesis/release of a vasoconstricting eicosanoid
by the endothelium [67]. Additionally, A vasodilating property of
rat aortic rings by Spirulina possibly dependent upon a
cyclooxygenase-dependent product of arachidonic acid and nitric
oxide has been reported by another study [68]. Decreasing NT-
proBNP levels may be an indicator of the efficacy of treatment
with Amlodipine or Spirulina on improving RV function and
reducing cardiac load in thalassemic patients.
In this study, no correlation was found between troponin I and
cardiac T2*, consistent with another study that showed no corre-
lation between troponin I and cardiac function (chest X-rays, ECG,
and echocardiography). Moreover, that study showed that troponin
I isn’t helpful for recognition of cardiac involvement in TM [69].
The present study showed no significant correlation between
serum ferritin and cardiac T2*. Though ferritin level has some
implication on the cardiac iron, it does not have a linear relation-
ship with the myocardial iron load. This result was in agreement
with several studies [30,70e74].
This poor correlation between serum ferritin and cardiac
T2*could be explained by many factors. First, ferritin is an acute
phase reactant that can be affected by common clinical conditions.
For example, ferritin levels may be increased by inflammation or
infection (especially in hepatitis C, which is highly prevalent
worldwide in adult TM) and may be decreased by vitamin C defi-
ciency [1]. Additionally, Serum ferritin only reflects stored iron that
is in transition in the blood (1% of the total iron storage pool) [30].
The preference of Amlodipine among the calcium channel
blockers is derived from both, its safety profile (including pediatric
populations) [75], as well as its ability to maintain an advantageous
balance between blockade of myocardial LTCC without extreme SA
and AV nodal blockade triggering bradyarrhythmias, a widespread
complication of iron overload. This could extend the use of the drug
in patients with left ventricular dysfunction, a condition in TM
patients where cardiac iron overload is usually more significant.
Amlodipine also possess anti-oxidant properties which are bene-
ficial due to the pivotal role of oxidative stress in iron-overload
cardiomyopathy, so Amlodipine represents an ideal CCB to be
used in patients with iron-overload cardiomyopathy [13].
The drawbacks of this study could be the small sample size in
each group, attributed to the low prevalence of TM patients in
Tanta, in addition to, the short follow-up period of 3 months, and
the lack of a placebo control.
5. Conclusion
The use of a calcium channel blocker Amlodipine or Spirulina in
addition to standard chelation therapy could be beneficial in
reducing cardiac iron overload in patients with thalassemia major,
thus improving survival and quality of life. These outcomes may be
a motivational step for further trials on a large scale and longer
follow-up period.
Conflicts of interest
The authors declare that there is no conflict of interests
regarding the publication of this paper.
Acknowledgments
The authors thank Maysa El-nagar, Esraa Mosalam and, Amal El-
haw for their contributions in conducting this study.
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