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Published in: Cardiovascular Toxicology 1/2024

18-12-2023 | Thalassemia | Research

Four‑Dimensional Echocardiographic Evaluation of Cardiac Iron Overload in Patients with Beta-Thalassemia Major

Authors: Ahmet Burak Fedai, Ugur Nadir Karakulak, Elifcan Aladag, Nilgun Sayinalp

Published in: Cardiovascular Toxicology | Issue 1/2024

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Abstract

Cardiac magnetic resonance imaging is the gold standard to detect cardiac iron overload in patients with beta-thalassemia. The aim of this study was to evaluate cardiac iron overload using four-dimensional transthoracic echocardiography in thalassemia patients with and without cardiac involvement detected by T2* value and to compare the two techniques. This cross-sectional and observational study was conducted in 44 patients diagnosed with thalassemia major. Left ventricular systolic function was assessed using four-dimensional speckle tracking echocardiography-derived global longitudinal (GLS), circumferential, radial, and area strain indices. Left ventricular ejection fraction, volumes, and mass index were similar between the patients with T2* values less than 20 ms as compared to those with T2* values greater than 20 ms. However, patients with lower T2* values had significantly higher GLS values (− 17.0% vs. − 19.8%, p < 0.001) compared with those with higher T2* values. GLS demonstrated a sensitivity of 91.7% and a specificity of 71.9% at a cut-off value of − 18.5%; however, sensitivity was 75%, and the specificity was 84.4% at a cut-off value of − 17.5%. For − 18.5%, the positive predictive value was 55%, and the negative predictive value was 95.8%; for − 17.5%, these values were 64.2 and 90%, respectively. This novel echocardiographic method, tested for the first time in our study in comparison with cardiac MRI in an adult patient group, has been shown to predict cardiac iron overload in thalassemia patients in the subclinical period without LVEF decline. Four-dimensional GLS is a marker with high sensitivity and negative predictive value.
Literature
1.
go back to reference Borgna-Pignatti, C., Rugolotto, S., De Stefano, P., Zhao, H., Cappellini, M. D., Del Vecchio, G. C., Romeo, M. A., Forni, G. L., Gamberini, M. R., Ghilardi, R., Piga, A., & Cnaan, A. (2004). Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica, 89(10), 1187–1193.PubMed Borgna-Pignatti, C., Rugolotto, S., De Stefano, P., Zhao, H., Cappellini, M. D., Del Vecchio, G. C., Romeo, M. A., Forni, G. L., Gamberini, M. R., Ghilardi, R., Piga, A., & Cnaan, A. (2004). Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica, 89(10), 1187–1193.PubMed
4.
go back to reference Nadar, S. K., Daar, S., Abdelmottaleb, W. A., Shaikh, M. M., Al Mahrouqi, H., Al-Raiisi, M., Hassan, M., Al Rawahi, B., & Al Rahbi, S. (2021). Abnormal diastolic function and global longitudinal strain in patients with Thalassemia Major on long term chelation therapy. International Journal of Cardiovascular Imaging, 37(2), 643–649. https://doi.org/10.1007/s10554-020-02036-8CrossRefPubMed Nadar, S. K., Daar, S., Abdelmottaleb, W. A., Shaikh, M. M., Al Mahrouqi, H., Al-Raiisi, M., Hassan, M., Al Rawahi, B., & Al Rahbi, S. (2021). Abnormal diastolic function and global longitudinal strain in patients with Thalassemia Major on long term chelation therapy. International Journal of Cardiovascular Imaging, 37(2), 643–649. https://​doi.​org/​10.​1007/​s10554-020-02036-8CrossRefPubMed
5.
go back to reference Karakulak, U. N., Aladag, E., Hekimsoy, V., Sahiner, M. L., Kaya, E. B., Ozer, N., Aksu, S., Demiroglu, H., Goker, H., Buyukasik, Y., Ozcebe, O., Sayinalp, N., & Haznedaroglu, I. C. (2021). Four-dimensional echocardiographic evaluation of left ventricular systolic functions in patients with chronic myeloid leukaemia receiving tyrosine kinase inhibitors. Cardiovascular Toxicology, 21(3), 216–223. https://doi.org/10.1007/s12012-020-09613-2CrossRefPubMed Karakulak, U. N., Aladag, E., Hekimsoy, V., Sahiner, M. L., Kaya, E. B., Ozer, N., Aksu, S., Demiroglu, H., Goker, H., Buyukasik, Y., Ozcebe, O., Sayinalp, N., & Haznedaroglu, I. C. (2021). Four-dimensional echocardiographic evaluation of left ventricular systolic functions in patients with chronic myeloid leukaemia receiving tyrosine kinase inhibitors. Cardiovascular Toxicology, 21(3), 216–223. https://​doi.​org/​10.​1007/​s12012-020-09613-2CrossRefPubMed
6.
go back to reference Fang, S., Zhang, Z., Wang, Y., Jiang, F., Yang, K., He, F., & Zhang, C. (2019). Predictive value of left ventricular myocardial strain by four-dimensional speckle tracking echocardiography combined with red cell distribution width in heart failure with preserved ejection fraction. Echocardiography, 36(6), 1074–1083. https://doi.org/10.1111/echo.14373CrossRefPubMed Fang, S., Zhang, Z., Wang, Y., Jiang, F., Yang, K., He, F., & Zhang, C. (2019). Predictive value of left ventricular myocardial strain by four-dimensional speckle tracking echocardiography combined with red cell distribution width in heart failure with preserved ejection fraction. Echocardiography, 36(6), 1074–1083. https://​doi.​org/​10.​1111/​echo.​14373CrossRefPubMed
7.
go back to reference Lang, R. M., Bierig, M., Devereux, R. B., Flachskampf, F. A., Foster, E., Pellikka, P. A., Picard, M. H., Roman, M. J., Seward, J., Shanewise, J. S., Solomon, S. D., Spencer, K. T., Sutton, M. S., Stewart, W. J., Chamber Quantification Writing, G., American Society of Echocardiography’s, G., Standards, C., & European Association of, E. (2005). Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. Journal of the American Society of Echocardiography, 18(12), 1440–1463. https://doi.org/10.1016/j.echo.2005.10.005CrossRefPubMed Lang, R. M., Bierig, M., Devereux, R. B., Flachskampf, F. A., Foster, E., Pellikka, P. A., Picard, M. H., Roman, M. J., Seward, J., Shanewise, J. S., Solomon, S. D., Spencer, K. T., Sutton, M. S., Stewart, W. J., Chamber Quantification Writing, G., American Society of Echocardiography’s, G., Standards, C., & European Association of, E. (2005). Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. Journal of the American Society of Echocardiography, 18(12), 1440–1463. https://​doi.​org/​10.​1016/​j.​echo.​2005.​10.​005CrossRefPubMed
9.
go back to reference Lang, R. M., Badano, L. P., Tsang, W., Adams, D. H., Agricola, E., Buck, T., Faletra, F. F., Franke, A., Hung, J., de Isla, L. P., Kamp, O., Kasprzak, J. D., Lancellotti, P., Marwick, T. H., McCulloch, M. L., Monaghan, M. J., Nihoyannopoulos, P., Pandian, N. G., Pellikka, P. A., et al. (2012). EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. European Heart Journal Cardiovascular Imaging, 13(1), 1–46. https://doi.org/10.1093/ehjci/jer316CrossRefPubMed Lang, R. M., Badano, L. P., Tsang, W., Adams, D. H., Agricola, E., Buck, T., Faletra, F. F., Franke, A., Hung, J., de Isla, L. P., Kamp, O., Kasprzak, J. D., Lancellotti, P., Marwick, T. H., McCulloch, M. L., Monaghan, M. J., Nihoyannopoulos, P., Pandian, N. G., Pellikka, P. A., et al. (2012). EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. European Heart Journal Cardiovascular Imaging, 13(1), 1–46. https://​doi.​org/​10.​1093/​ehjci/​jer316CrossRefPubMed
10.
go back to reference Solmaz, H., Cabuk, A. K., Altin, Z., Albudak Ozcan, E., & Ozdogan, O. (2021). Left ventricular systolic dyssynchrony index and endothelial dysfunction parameters as subclinical predictors of cardiovascular involvement in patients with beta-thalassemia major. Echocardiography, 38(6), 825–833. https://doi.org/10.1111/echo.15067CrossRefPubMed Solmaz, H., Cabuk, A. K., Altin, Z., Albudak Ozcan, E., & Ozdogan, O. (2021). Left ventricular systolic dyssynchrony index and endothelial dysfunction parameters as subclinical predictors of cardiovascular involvement in patients with beta-thalassemia major. Echocardiography, 38(6), 825–833. https://​doi.​org/​10.​1111/​echo.​15067CrossRefPubMed
11.
go back to reference Agha, H. M., AbdelMassih, A. F., AbdelRahman, M. Y., Milanesi, O., Castaldi, B., Geranio, G., Putti, M. C., Kharabish, A., Esmail, R., El-Kamah, G., Hamdy, M., El-Baz, H., Behairy, N., Hanna, C., El-Tagy, H., Mishriky, M. A., Mamdouh, M., Antonazzo, L., & Ramadan, T. (2018). Can myocardial remodeling be a useful surrogate predictor of myocardial iron load? A 3D echocardiographic multicentric study. Pediatric Blood & Cancer, 65(10), e27272. https://doi.org/10.1002/pbc.27272CrossRef Agha, H. M., AbdelMassih, A. F., AbdelRahman, M. Y., Milanesi, O., Castaldi, B., Geranio, G., Putti, M. C., Kharabish, A., Esmail, R., El-Kamah, G., Hamdy, M., El-Baz, H., Behairy, N., Hanna, C., El-Tagy, H., Mishriky, M. A., Mamdouh, M., Antonazzo, L., & Ramadan, T. (2018). Can myocardial remodeling be a useful surrogate predictor of myocardial iron load? A 3D echocardiographic multicentric study. Pediatric Blood & Cancer, 65(10), e27272. https://​doi.​org/​10.​1002/​pbc.​27272CrossRef
12.
go back to reference Li, S. J., Hwang, Y. Y., Ha, S. Y., Chan, G. C., Mok, A. S., Wong, S. J., & Cheung, Y. F. (2016). Role of three-dimensional speckle tracking echocardiography in the quantification of myocardial iron overload in patients with beta-thalassemia major. Echocardiography, 33(9), 1361–1367. https://doi.org/10.1111/echo.13266CrossRefPubMed Li, S. J., Hwang, Y. Y., Ha, S. Y., Chan, G. C., Mok, A. S., Wong, S. J., & Cheung, Y. F. (2016). Role of three-dimensional speckle tracking echocardiography in the quantification of myocardial iron overload in patients with beta-thalassemia major. Echocardiography, 33(9), 1361–1367. https://​doi.​org/​10.​1111/​echo.​13266CrossRefPubMed
13.
go back to reference Eroglu, A. G., Ulug, N., Karakas, H., Yuksel, E. K., Akyel, N. G., Cig, G., Adaletli, I., Ozdemir, G. N., Turkkan, E., & Celkan, T. T. (2022). Evaluation of left ventricular function and myocardial deformation in children with beta-thalassemia major by real-time three-dimensional (four-dimensional) and speckle tracking echocardiography. Echocardiography, 39(10), 1307–1315. https://doi.org/10.1111/echo.15453CrossRefPubMed Eroglu, A. G., Ulug, N., Karakas, H., Yuksel, E. K., Akyel, N. G., Cig, G., Adaletli, I., Ozdemir, G. N., Turkkan, E., & Celkan, T. T. (2022). Evaluation of left ventricular function and myocardial deformation in children with beta-thalassemia major by real-time three-dimensional (four-dimensional) and speckle tracking echocardiography. Echocardiography, 39(10), 1307–1315. https://​doi.​org/​10.​1111/​echo.​15453CrossRefPubMed
14.
go back to reference El Razaky, O. A., El-Shanshory, M. R., El-Shehaby, W. A., Hables, N. M., Elshamia, A. M., Fayed, A. M., El-Kholy, A. E., & El-Dosoky, E. A. (2019). Left ventricular regional function in children with beta thalassemia with no cardiac manifestations (four-dimensional echocardiographic study). Indian Journal of Hematology and Blood Transfusion, 35(4), 750–757. https://doi.org/10.1007/s12288-019-01117-6CrossRefPubMedPubMedCentral El Razaky, O. A., El-Shanshory, M. R., El-Shehaby, W. A., Hables, N. M., Elshamia, A. M., Fayed, A. M., El-Kholy, A. E., & El-Dosoky, E. A. (2019). Left ventricular regional function in children with beta thalassemia with no cardiac manifestations (four-dimensional echocardiographic study). Indian Journal of Hematology and Blood Transfusion, 35(4), 750–757. https://​doi.​org/​10.​1007/​s12288-019-01117-6CrossRefPubMedPubMedCentral
15.
go back to reference Pennell, D. J., Udelson, J. E., Arai, A. E., Bozkurt, B., Cohen, A. R., Galanello, R., Hoffman, T. M., Kiernan, M. S., Lerakis, S., Piga, A., Porter, J. B., Walker, J. M., Wood, J., American Heart Association Committee on Heart, F., Transplantation of the Council on Clinical, C., Council on Cardiovascular, R., & Imaging. (2013). Cardiovascular function and treatment in beta-thalassemia major: A consensus statement from the American Heart Association. Circulation, 128(3), 281–308. https://doi.org/10.1161/CIR.0b013e31829b2be6CrossRefPubMed Pennell, D. J., Udelson, J. E., Arai, A. E., Bozkurt, B., Cohen, A. R., Galanello, R., Hoffman, T. M., Kiernan, M. S., Lerakis, S., Piga, A., Porter, J. B., Walker, J. M., Wood, J., American Heart Association Committee on Heart, F., Transplantation of the Council on Clinical, C., Council on Cardiovascular, R., & Imaging. (2013). Cardiovascular function and treatment in beta-thalassemia major: A consensus statement from the American Heart Association. Circulation, 128(3), 281–308. https://​doi.​org/​10.​1161/​CIR.​0b013e31829b2be6​CrossRefPubMed
16.
18.
go back to reference Barbero, U., Fornari, F., Gagliardi, M., Fava, A., Giorgi, M., Alunni, G., Gaglioti, C. M., Piga, A., Ferrero, G. B., & Longo, F. (2021). Myocardial longitudinal strain as the first herald of cardiac impairment in very early iron overload state: An echocardiography and biosusceptometry study on beta-thalassemia patients. American Journal of Cardiovascular Diseases, 11(5), 555–563. Barbero, U., Fornari, F., Gagliardi, M., Fava, A., Giorgi, M., Alunni, G., Gaglioti, C. M., Piga, A., Ferrero, G. B., & Longo, F. (2021). Myocardial longitudinal strain as the first herald of cardiac impairment in very early iron overload state: An echocardiography and biosusceptometry study on beta-thalassemia patients. American Journal of Cardiovascular Diseases, 11(5), 555–563.
19.
go back to reference Pizzino, F., Meloni, A., Terrizzi, A., Casini, T., Spasiano, A., Cosmi, C., Allo, M., Zito, C., Carerj, S., Aquaro, G. D., Di Bella, G., & Pepe, A. (2018). Detection of myocardial iron overload by two-dimensional speckle tracking in patients with beta-thalassaemia major: A combined echocardiographic and T2* segmental CMR study. International Journal of Cardiovascular Imaging, 34(2), 263–271. https://doi.org/10.1007/s10554-017-1219-7CrossRefPubMed Pizzino, F., Meloni, A., Terrizzi, A., Casini, T., Spasiano, A., Cosmi, C., Allo, M., Zito, C., Carerj, S., Aquaro, G. D., Di Bella, G., & Pepe, A. (2018). Detection of myocardial iron overload by two-dimensional speckle tracking in patients with beta-thalassaemia major: A combined echocardiographic and T2* segmental CMR study. International Journal of Cardiovascular Imaging, 34(2), 263–271. https://​doi.​org/​10.​1007/​s10554-017-1219-7CrossRefPubMed
Metadata
Title
Four‑Dimensional Echocardiographic Evaluation of Cardiac Iron Overload in Patients with Beta-Thalassemia Major
Authors
Ahmet Burak Fedai
Ugur Nadir Karakulak
Elifcan Aladag
Nilgun Sayinalp
Publication date
18-12-2023
Publisher
Springer US
Published in
Cardiovascular Toxicology / Issue 1/2024
Print ISSN: 1530-7905
Electronic ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-023-09813-6

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