Combinatorial approach to treat iron overload cardiomyopathy in pediatric patients with thalassemia-major: A systematic review and meta-analysis

Figure 1  Study selection flow diagram (PRISMA chart).

Figure 2 Risk of bias assessment graph. The symbols used represent as follows: “+”: Low risk of bias; “-”: High risk of bias; “?”: Unclear risk of bias.

Figure 3 Forest plot showing changes in cardiac T2, myocardial iron concentration, and liver iron concentration. A: Forest plot showing changes in cardiac T2 with adding amlodipine to chelation therapy compared to chelation therapy alone, from baseline to follow-up. The analysis revealed a significant improvement in cardiac T2 in the amlodipine group, with a mean difference of 2.79 ms and a 95% confidence interval (CI) of 0.34 to 5.24 ms. The heterogeneity between the studies, assessed using the I² statistic, was 0%, indicating no variability in the outcome across the included studies; B: The forest plot illustrates changes in myocardial iron concentration between the amlodipine group and the control from baseline to follow-up. The analysis demonstrated a significant decrease in myocardial iron concentration within the amlodipine group, with a mean reduction of 0.31 and a 95%CI ranging from -0.38 to -0.25. Additionally, the heterogeneity among the studies, evaluated through the I² statistic, was 0%, indicating no variability in outcomes across the included studies; C: The forest plot illustrates the changes in liver iron concentration observed in the amlodipine group compared to the control group from baseline to follow-up. The analysis revealed a non-significant reduction in liver iron concentration within the amlodipine group, with a mean decrease of 0.04 and a 95%CI ranging from -0.33 to 0.24. Furthermore, the heterogeneity among the studies, assessed using the I² statistic, was determined to be 0%, indicating no variability in the outcomes across the studies included. CI: Confidence interval.

Figure 4 The forest plot of serum ferritin levels and reported adverse events. A: The forest plot illustrates the non-significant changes in serum ferritin levels observed in the amlodipine group compared to the control group from baseline to follow-up. The analysis indicated that amlodipine resulted in a non-significant reduction in serum ferritin, with a mean decrease of 328.86 and a 95% confidence interval ranging from -1212.34 to 554.62. The heterogeneity among the studies, evaluated using the I² statistic, was found to be 90%, which suggests a high level of variability in the outcomes across the included studies; B: The forest plot illustrates the odds ratio for reported adverse events, including gastrointestinal upset, hypotension, and lower limb edema, in the amlodipine group compared to the control group. The analysis demonstrated a statistically non-significant increased risk of adverse events in the amlodipine group, with an odds ratio of 2.17 and a 95% confidence interval ranging from 0.34 to 13.79. The heterogeneity among the studies, evaluated using the I² statistic, was found to be 58%, indicating moderate variability in outcomes across the included studies. CI: Confidence interval; GI: Gastrointestinal.