TALASEMİ MAJORLÜ ÇOCUK VE GENÇ YETİŞKİNLERDE DEMİR YÜKÜ İLE YAŞ VE KARDİYAK FONKSİYONLARIN İLİŞKİSİNİN DEĞERLENDİRİLMESİ: BİR DARBELİ DOPPLER VE DOKU DOPPLER GÖRÜNTÜLEME ÇALIŞMASI

Öz

Amaç: Darbeli dalga Doppler ve doku Doppler görüntüleme yöntemleri kullanılarak talasemi majorlu (TM) çocuk ve genç yetişkinlerde sağlıklı kişilere göre kardiyak yapısal ve fonksiyonel farklılıklarının belirlenmesi; demir yükünün bu farklılıklar ile olan ilişkisinin ortaya konması amaçlanmıştır. Gereç ve Yöntem: Çalışmamızı yaşları 4-22 arasında olan çocuk ve genç yetişkin TM lü hastaların (n=44) ve yaş-cinsiyet uyumlu kontrol grubunun (n=40) hastanemiz veri sistemindeki 01.10.2023 ile 01.10.2024 tarihleri arasındaki verilerinin incelenmesiyle oluşturduk. Hastaların boy, kilo, vücut kitle indexi (VKI), sistolik-diyastolik kan basıncı ölçümleri ile tam kan sayımı, ferritin, kardiyak T2*MRI değerleri ve ekokardiyografi kayıtları kaydedildi. İki grup arasında karşılaştırmaların yanısıra; ve TM hastalarında ferritin-kardiyak T2*MRI sonuçları ile ekokardiyografik parametreler-yaş arasında korelasyon analizi yapıldı. Bulgular: Çalışmamızda TM hastalarında büyüme gelişme geriliği (boy SDS, kilo SDS ve VKI SDS düşük), sol boşluklarda dilatasyon (LVIDd yüksek), sol ventrikül kas kitlesinde artış (LVMI yüksek), kardiyak aşikar diyastolik (restriktif özellikte olan: LV tepe erken diyastolik akımı (E)/tepe geç diyastolik akımı (A) ve E/erken diyastolik miyokardiyal tepe akımı (E') yüksek) ve subklinik sistolik (LV tepe sistolik akımı (Sm) düşük ve LV Tei indexi (TX) yüksek) fonksiyon bozukluğu olduğunu tespit ettik. Bununla birlikte demir yükü (ferritin ve kardiyak T2*MRI) ile LVMI, kardiyak diyastolik ve sistolik fonksiyon göstergeleri arasında ilişki mevcuttu. Yaş arttıkça ferritin değeri değişmezken kardiyak T2*MRI değerinin azaldığı; diyastolik ve sistolik parametrelerde kötüleşmelerin olduğu tespit edildi. Sonuç: TM lü hastaların periyodik olarak kardiyak T2*MRI ile doppler ekokardiyografi incelemelerinin yapılmasıyla subklinik myokardiyal disfonksiyon erken dönemde tespit edilebilir; bu da bize gerekli müdahelelerin yapılması açısından fırsat penceresi sunabilir.

Anahtar Kelimeler

• talasemi
• kardiyak fonksiyonlar
• aşırı demir yükü
• kardiyak T2 MR,
• Doppler ekokardiyografi

EVALUATION OF THE RELATIONSHIP BETWEEN IRON LOAD, AGE, AND CARDIAC FUNCTION IN CHILDREN AND YOUNG ADULTS WITH THALASSEMIA MAJOR: A PULSED-WAVE DOPPLER AND TISSUE DOPPLER IMAGING STUDY

Öz

Objective: To determine the structural and functional cardiac differences in children and young adults with thalassemia major (TM) compared to healthy subjects using pulsed-wave Doppler and tissue Doppler imaging methods and determine the relationship between iron overload and these differences. Materials and Methods: We analyzed the data of pediatric and young adult TM patients (n = 44) aged 4–22 years and an age- and gender-matched control group (n = 40) in our hospital data system between Oct.01.2023 and Oct.01.2024. Height, weight, body mass index (BMI), systolic–diastolic blood pressure measurements, complete blood count, ferritin, cardiac T2* magnetic resonance imaging (MRI) values, and echocardiography results were recorded. In addition to comparisons between the two groups, correlation analysis was performed between ferritin–cardiac T2* MRI results and echocardiographic parameters and age in TM patients. Results: Our study showed growth retardation (low height standard deviation score (SDS), low weight SDS and low BMI SDS), dilatation of the left cavities (high left ventricular internal diameter end diastole (LVIDd)), increased left ventricular muscle mass (high left ventricular mass index (LVMI)), cardiac distinctive diastolic (restrictive pattern: left ventricular (LV) peak early diastolic flow (E)/peak late diastolic flow (A) and E/early diastolic myocardial peak flow (E') high), and subclinical systolic (LV peak systolic flow low and LV Tei index high) dysfunction. In addition, iron load (ferritin and cardiac T2* MRI) was correlated with LVMI, and cardiac diastolic and systolic function indicators. As age increased, ferritin value did not change, but cardiac T2* MRI value decreased and diastolic–systolic parameters worsened. Conclusion: Periodic cardiac T2* MRI and Doppler echocardiography examinations of patients with TM may detect subclinical myocardial dysfunction at an early stage, thus providing a window of opportunity for intervention.

Anahtar Kelimeler

• thalassemia
• cardiac functions
• iron overload
• cardiac T2 MRI
• Doppler echocardiography

Kaynakça

1. 1- Carsote M, Vasiliu C, Trandafir AI, et al. New Entity-Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement. Diagnostics (Basel). 2022 Aug 9;12(8):1921. doi: 10.3390/diagnostics12081921. PMID: 36010271; PMCID: PMC9406368.
2. 2- Yousuf R, Akter S, Wasek SM, et al. Thalassemia: A Review of the Challenges to the Families and Caregivers. Cureus. 2022 Dec 13;14(12):e32491. doi: 10.7759/cureus.32491. PMID: 36523854; PMCID: PMC9747324.
3. 3- An Q, Fan C, Xu S. Recent perspectives of pediatric β-thalassemia. Minerva Pediatr (Torino). 2022 Jun;74(3):365-72. doi: 10.23736/S2724-5276.18.04872-7. Epub 2018 Feb 23. PMID: 29479942.
4. 4- Das B, Deshpande S, Akam-Venkata J, et al. Heart Failure with Preserved Ejection Fraction in Children. Pediatr Cardiol. 2023 Mar;44(3):513-529. doi: 10.1007/s00246-022-02960-7. Epub 2022 Aug 17. PMID: 35978175.
5. 5- Pepe A, Positano V, Santarelli MF, et al. Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload. J Magn Reson Imaging. 2006 May;23(5):662-8. doi: 10.1002/jmri.20566. PMID: 16568436.
6. 6- Kirk P, Roughton M, Porter JB, et al. Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major. Circulation. 2009 Nov 17;120(20):1961-8. doi:10.1161/CIRCULATIONAHA.109.874487. Epub 2009 Oct 2. PMID: 19801505; PMCID: PMC2784198.
7. 7- Lang RM, Badano LP, Mor‑Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of cardiovascular ımaging. J Am Soc Echocardiogr 2015;28:1‑39.e14. doi: 10.1016/j.echo.2014.10.003.
8. 8- Askin L, Yuce Eİ, Tanriverdi O. Myocardial performance index and cardiovascular diseases. Echocardiography 2023;40:720‑5.

9. 9- Kattamis A, Forni G.L, Aydinok Y, et al. Changing patterns in the epidemiology of -thalassemia. Eur. J. Haematol.2020, 105, 692–703.
10. 10- Demir Yenigurbuz F, Akıncı B, Üstyol A, et al. Endocrine Complications in Pediatric Beta-Thalassemia Major Patients: A Single-Center Experience. Harran Üniversitesi Tıp Fakültesi Dergisi. 2022;19(3):556-62. doi: 10.35440/hutfd.1144199.
11. 11- Topuz, Emek vd. “Outcomes of Late Endocrinologic Evaluation in Adult Patients With Thalassemia Major: Case Series”. Cukurova Medical Journal, c. 49, sy. 3, 2024, ss. 834-40, doi:10.17826/cumj.1405545.
12. 12- Fianza PI, Pramono AA, Ghozali M, et al. Diagnostic Modalities in Detecting Cardiovascular Complications of Thalassemia. Rev Cardiovasc Med. 2022 Jul 22;23(8):267. doi: 10.31083/j.rcm2308267. PMID: 39076648; PMCID: PMC11266957.
13. 13- Garadah TS, Mahdi N, Kassab S, et al. The pro-BNP Serum level and echocardiographic tissue Doppler abnormalities in patients with beta thalassemia major. Cardiology 2010;4:135–41.
14. 14- Akpinar O, Acarturk E, Kanadasi M, et al. Tissue Doppler imaging and NT-proBNP levels show the early impairment of ventricular function in patients with ß-thalassemia major. Acta Cardiologica 2007;62:225–31.
15. 15- Deraz SE, Abd El Naby SA, Mahmoud AA. Assessment of ventricular dysfunction in Egyptian children with Beta-thalassemia major. Hematol Oncol Stem Cell Ther. 2021 Sep;14(3):206-13. doi: 10.1016/j.hemonc.2020.07.003. Epub 2020 Jul 30. PMID: 32758485.
16. 16- Murphy CJ, Oudit GY. Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. J Card Fail 2010;16:888–900.
17. 17- Kumfu S, Chattipakorn SC, Chattipakorn N. Iron overload cardiomyopathy: Using the latest evidence to inform future applications. Exp Biol Med (Maywood). 2022 Apr;247(7):574-583. doi: 10.1177/15353702221076397.
18. 18- Tan JY, Yeo YH, Chan KH, et al. Causes of Death and Mortality Trends in Individuals with Thalassemia in the United States, 1999-2020. J Blood Med. 2024 Aug 5;15:331-9. doi: 10.2147/JBM.S470177. PMID: 39132283; PMCID: PMC11315644.
19. 19- Russo V, Melillo E, Papa AA, et al. Arrhythmias and Sudden Cardiac Death in Beta-Thalassemia Major Patients: Noninvasive Diagnostic Tools and Early Markers. Cardiol Res Pract. 2019 Nov 30;2019:9319832. doi: 10.1155/2019/9319832. PMID: 31885907; PMCID: PMC6914907.
20. 20- Sahin C, Basaran O, Altun I, et al. Assessment of Myocardial Performance Index and Aortic Elasticity in Patients With Beta-Thalassemia Major. J Clin Med Res. 2015 Oct;7(10):795-801. doi: 10.14740/jocmr2293w. Epub 2015 Aug 23. PMID: 26346439; PMCID: PMC4554220.
21. 21- Chen MR, Ko HS, Chao TF, et al. Relation of myocardial systolic mechanics to serum ferritin level as a prognosticator in thalassemia patients undergoing repeated transfusion. Echocardiography. 2015 Jan;32(1):79-88. doi: 10.1111/echo.12590. Epub 2014 Mar 27. PMID: 24673419.
22. 22- Aessopos A, Deftereos S, Tsironi M, et al. Predictive echo-Doppler indices of left ventricular impairment in b-thalassemic patients. Annals Hematology 2007;86:429–34.
23. 23- Ommen SR, Nishimura RA, Appleton CP. Clinical utility of Doppler chocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressure: a comparative simultaneous Doppler catheterization study. Circulation 2000;102:1788–94.
24. 24- Nanjegowda CK, Kamath SP, Kamath P, et al. Comparison of diastolic function in children with transfusion dependent beta thalassemia major by tissue and conventional doppler imaging indices and its correlation with serum ferritin levels. Turk J Pediatr. 2019;61(2):250-6. doi: 10.24953/turkjped.2019.02.014. PMID: 31951335.
25. 25- Yavuz T, Nisli K, Oner N, et al. Assessment of diastolic function in children and adolescents with beta-thalassemia major by tissue Doppler imaging. Turk Arch Pediatr 2011; 46: 27-32. DOI: 10.4274/tpa.46.05
26. 26- Salama K, Abdelsalam A, Eldin HS, et al. The relationships between pancreatic T2* values and pancreatic iron loading with cardiac dysfunctions, hepatic and cardiac iron siderosis among Egyptian children and young adults with β-thalassaemia major and sickle cell disease: a cross-sectional study. F1000Res. 2020 Sep 9;9:1108. doi: 10.12688/f1000research.25943.2. PMID: 34249348; PMCID: PMC8261758.
27. 27- Silvilairat S, Charoenkwan P, Saekho S, et al. Early detection of ventricular dysfunction by tissue Doppler echocardiography related to cardiac iron overload in patients with thalassemia. Int J Cardiovasc Imaging. 2021 Jan;37(1):91-8. doi: 10.1007/s10554-020-01949-8. Epub 2020 Jul 29. PMID: 32728990.
28. 28- El-Shanshory M, Tolba O, El-Shafiey R, et al. Cardiac Iron Overload by MRI in Children With B-Thalassemia Major and its Correlation With Cardiac Function by Echocardiography. J Pediatr Hematol Oncol. 2020 Aug;42(6):398-402. doi: 10.1097/MPH.0000000000001786. PMID: 32251156.
29. 29- Darvishi-Khezri H, Aliasgharian A, Naderisorki M, et al. Ferritin thresholds for cardiac and liver hemosiderosis in β-thalassemia patients: a diagnostic accuracy study. Sci Rep. 2022 Oct 26;12(1):17996. doi: 10.1038/s41598-022-22234-9. PMID: 36289264; PMCID: PMC9606378.
30. 30- Güzelbey T, Gürses B, Sarsılmaz A, et al. Talasemi Majör Hastalarında MRG ile Kardiyak Demir Yükü Ölçümü, Demir Yükünün Kardiyak Fonksiyonlara Etkisinin Değerlendirilmesi ve Doku Doppleri ile Karşılaştırılması. IGUSABDER. 2024;:81–96. doi:10.38079/igusabder.1362022.