THE DIAGNOSTIC VALUE OF PULSED WAVE TISSUE DOPPLER IMAGING IN ASYMPTOMATIC BETA- THALASSEMIA MAJOR CHILDREN AND YOUNG ADULTS ; RELATION TO CHEMICAL BIOMARKERS OF LEFT VENTRICULAR FUNCTION AND IRON OVERLOAD .
Main Article Content
Keywords
Beta-thalassemia, Tissue Doppler imaging, Myocardial function, Biomarkers
Abstract
Background: Cardiac iron toxicity is the leading cause of death among ?-halassaemia major (TM) patients. Once heart failure becomes overt , it will be difficult to reverse . Objectives: To investigate non overt cardiac dysfunctions in TM patients using pulsed wave Tissue Doppler Imaging (TD I) and its relation to the iron overload and brain natruritic peptide (BNP). Methods: Thorough clinical , conventional echo and pulsed wave TDI parameters were compared between asymtomatic 25 ?-TM patients and 20 age and gender matched individuals. Serum ferritin and plasma BNP levels were assayed by ELISA . Results: TM patients had significant higher mitral inflow early diastolic (E) wave and non significant other conventional echo parameters. Pulsed wave TDI revealed systolic and diastolic dysfunctions in the form of significant higher isovolumetric contraction time (ICT) , ejection time ( E T) and isovolumetric relaxation time (IRT) with significantly lower mitral annulus early diastolic velocity E` (12.07 ±2.06 vs 15.04±2.65 ,P= 0.003) in patients compared to controls. Plasma BNP was higher in patients compared to the controls. Plasma BNP and serum ferritin had significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions. Patients with E/E` ? 8 had significant higher serum ferritin and plasma BNP levels compared to those with E/E` ratio < 8 without difference in Hb levels .Conclusion: Pulsed wave TDI is an important diagnostic tool for latent cardiac dysfunction in iron loaded TM patients and is related to iron overload and BNP .
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References
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8. Cohen AR, Galanello R, Pennell DJ, Cunningham MJ, Vichinsky E. Thalassemia. Hematology Am Soc Hematol Educ Program 2004:14-34.
9. Hahalis G, Manolis AS, Gerasimidou I, Alexopoulos D, Sitafidis G, Kourakli A. Right ventricular diastolic function in beta-thalassemia major: Echocardiographic and clinical correlates. Am Heart J. 2001;141:428–434.
10- Hamdy AM. Use of strain and tissue velocity imaging for early detection of regional myocardial dysfunction in patients with beta thalassemia. Eur J Echocardiogr. 2007 Mar;8(2):102-109.
11.Mottram PM, Marwick TH. Assessment of diastolic function: what the general cardiologist needs to know. Heart. 2005 May;91(5):681-695.
12. Leonardi B, Margossian R, Colan SD, Powell AJ. Relationship of magnetic resonance imaging estimation of myocardial iron to left ventricular systolic and diastolic function in thalassemia. JACC Cardiovasc Imaging. 2008 Sep;1(5):572-578.
13. Yu CM, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler imaging a new prognosticator for cardiovascular diseases. J Am Coll Cardiol. 2007 May 15;49(19):1903-1914.
14. Iarussi D, Di Salvo G, Pergola V, Coppolino P, Tedesco MA, Ratti G, Esposito L, Calabrò R, Ferrara M.. Pulsed doppler tissue imaging and myocardial function in thalassemia major. Heart Vessels. 2003 Mar;18(1):1-6.
15. Daniels LB, Maisel AS.Natriuretic Peptides. J Am Coll Cardiol. 2007 Dec 18;50(25):2357-2368.
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17.Sagnella GA. Measurement and importance of plasma brainnatriuretic peptide and related peptides. Ann Clin Biochem. 2001 Mar;38(Pt 2):83-93.
18. Kremastinos DT, Tsiapras DP, Kostopoulou AG, Hamodraka ES, Chaidaroglou AS, Kapsali ED. NT-proBNP levels and diastolic dysfunction in ?-thalassaemia major patients. Eur J Heart Fail. 2007 May;9(5):531-536.
19. Teichholz LE, Kreulen T, Herman MV, Gorlin R.Problems in
echocardiographic volume determinations: Echocardiographic -angiographic
correlations in the presence or absence of asynergy. Am J Cardiol. 1976 Jan;37(1):7-11.
20. Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc
Echocardiogr. 2007;20:1021–1041.
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23. Kremastinos DT, Toutouzas PK, Vyssoulis GP, Venetis CA, Vretou HP, Avgoustakis DG. Global and segmental left ventricular function in beta-thalassemia. Cardiology. 1985;72(3):129-139.
24.Aypar E1, Alehan D, Hazirolan T, Gümrük F.The efficacy of tissue Doppler imaging in predicting myocardial iron load in patients with beta-thalassemia major: correlation with T2* cardiovascular magnetic resonance.
Int J Cardiovasc Imaging. 2010 Apr;26(4):413-429.
25. Uçar T, Ileri T, Atalay S, Uysal Z, Tutar E, Ertem M.Early detection of myocardial dysfunction in children with beta-thalassaemia major. Int J Cardiovasc Imaging. 2009 Apr;25(4):379-386.
26. Ehlers KH, Levin AR, Markenson AL, Marcus JR, Klein AA,
Hilgartner MW, Engle MA (1980) Longitudinal study of cardiac function in thalassemia major. Ann N Y Acad Sci. 1980;344:397-404.
27.Kremastinos DT, Hamodraka E, Parissis J, Tsiapras D, Dima K, Maisel A. Predictive value of B-type natriuretic peptides in detecting latent left ventricular diastolic dysfunction in beta-thalassemia major. Am Heart J. 2010 Jan;159(1):68-74.
28.Parale GP, Pawar SS, Tapare VS. Assessment of LV diastolic function in patients with beta-thalassemia major with special reference to E/Eann ratio.
J Pediatr Hematol Oncol. 2009 Jan;31(1):69-73.
29.Abdelmoktader AM, Azer HY .Usefulness of pulsed wave tissue doppler imaging in assessment of left ventricular functions in children with beta-thalassemia major.
Indian J Pediatr. 2013 Sep;80(9):721-725.
30.Noori NM, Mehralizadeh S. Echocardiographic evaluation of systolic and diastolic heart function in patients suffering from beta-thalassemia major aged 5-10 years at the Zahedan Research Center for Children and Adolescent Health. Anadolu Kardiyol Derg. 2010 Apr;10(2):150-153.
31. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health
and disease: Doppler echocardiography is the clinician’s Rosetta Stone. J Am Coll Cardiol. 1997 Jul;30(1):8-18.
32.Agha HM, Beshlawy A, Hamdy M, Sobeih A, El Zahrae F, Abd El Satar IA, AbdelMassih A, Said F, Abd El Aziz O, El Tagui M, Pennell DJ. Early detection of right ventricular diastolic dysfunction by pulsed tissue Doppler echocardiography in iron loaded beta thalassemia patients. Pediatr Cardiol. 2015 Mar;36(3):468-474.
33. Seliem MA, Al-Saad HI, Bou-Holaigah IH, Khan MN, Palileo MR. Left ventricular diastolic dysfunction in congenital chronic anaemias during childhood as determined by comprehensive echocardiographic imaging including acoustic quantification.. Eur J Echocardiogr. 2002 Jun;3(2):103-110.
34. Garadah T, Kassab S, Mahdi N, Abu-Taleb A and Jamsheer A. Pulsed and Tissue Doppler Echocardiographic Changes in Patients with Thalassemia Major Clinical Medicine Insights: Cardiology 2010;3 :1–8.
35. Vaccari M, Crepaz R, Fortini M, Gamberini MR, Scarcia S, Pitscheider W, Bosi G. Left ventricular remodeling, systolic function, and diastolic function in young adults with beta thalassemia intermedia. Chest. 2002 Feb;121(2):506-512.
36. Fitchett DH, Coltart DJ, Littler WA, Leyland MJ, Trueman T, Gozzard DI, Peters TJ. Cardiac involvement in secondary haemochromatosis: a catheter biopsy study and analysis of myocardium. Cardiovasc Res. 1980 Dec;14(12):719-724.
37. Lattanzi F, Bellotti P, Picano E, Chiarella F, Mazzarisi A, Melevendi C, Forni G, Landini L, Distante A, Vecchio C. Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload. Circulation. 1993 Mar;87(3):748-754.
38. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW.Assessment of mitral annulus velocity by Doppler tissue
imaging in evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997 Aug;30(2):474-480.
39. Gharzuddine WS1, Kazma HK, Nuwayhid IA, Bitar FF, Koussa SF, Moukarbel GV, Taher AT. Doppler characterization of left ventricular diastolic function in beta-thalassaemia major. Evidence for an early stage of impaired relaxation. Eur J Echocardiogr. 2002 Mar;3(1):47-51.
40. Nagueh SF, Lakkis NM, Middleton KJ, Spencer WH 3rd, Zoghbi WA, Quiñones MA. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation. 1999 Jan 19;99(2):254-261.
41. Chrysohoou C, Greenberg M, Pitsavos C, Panagiotakos DB, Ladis V, Barbetseas J, Brili S, Singh S, Stefanadis C.. Diastolic function in young patients with beta- thalassemia major: an echocardiographic study. Echocardiography. 2006 Jan;23(1):38-44.
42.Nikolidakis S, Flessa C, Nikolaou N, Gotsis ED, Koutouzis M, Polyhronaki E, Vrettou E, Kyriakides ZS. Brain natriuretic peptide as marker of myocardial iron load in beta-thalassemia.Int J Cardiol. 2007 Jun 12;118(3):408-409.
43.Lo L, Singer ST . Thalassemia ; current approach to an old disease . Pediatr Clin North Am. 2002 Dec;49(6):1165-91, v.
44. Anderson LJ1, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ. Cardiovascular T2 star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001 Dec;22(23):2171-2179.
45. Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, Hoffman TM, Kiernan MS, Lerakis S, Piga A, Porter JB, Walker JM, Wood J; American Heart Association Committee on Heart Failure and Transplantation of the Council on Clinical Cardiology and Council on Cardiovascular Radiology and Imaging. Cardiovascular function and treatment in b-Thalassemia major: a consensus statement from the american heart association. Circulation. 2013 Jul 16;128(3):281-308.
2. TheinSL .Genetic modifiers of ?-thalassemia .Haematologica. 2005 May; 90(5):651-660.
3.Olivieri NF, Nathan DG, MacMillan JH, Wayne AS, Liu PP, McGee A, Martin M, Koren G, Cohen AR.Survival in medically treated patients with homozygous beta-Thalassemia. N Engl J Med. 1994 Sep 1;331(9):574-578.
4. Walker JM .The heart in thalassaemia. Eur Heart J.2002 23:102–105.
5. Borgna-Pignatti C, Cappellini MD, De Stefano P, Del Vecchio GC, Forni GL, Gamberini MR, Ghilardi R, Piga A, Romeo MA, Zhao H, Cnaan A. Cardiac morbidity and mortality in deferoxamineor deferiprone-treated patients with thalassemia major. Blood. 2006 May 1;107(9):3733-3737.
6.Kremastinos DT, Farmakis D, Aessopos A, Hahalis G, Hamodraka E, Tsiapras D, Keren A. Beta-thalassemia cardiomyopathy: history, present considerations, and future perspectives. Circ Heart Fail. 2010 May;3(3):451-458.
7. Pennell DJ . T2* magnetic resonance and myocardial iron in thalassemia. Ann N Y Acad Sci. 2005;1054:373-378.
8. Cohen AR, Galanello R, Pennell DJ, Cunningham MJ, Vichinsky E. Thalassemia. Hematology Am Soc Hematol Educ Program 2004:14-34.
9. Hahalis G, Manolis AS, Gerasimidou I, Alexopoulos D, Sitafidis G, Kourakli A. Right ventricular diastolic function in beta-thalassemia major: Echocardiographic and clinical correlates. Am Heart J. 2001;141:428–434.
10- Hamdy AM. Use of strain and tissue velocity imaging for early detection of regional myocardial dysfunction in patients with beta thalassemia. Eur J Echocardiogr. 2007 Mar;8(2):102-109.
11.Mottram PM, Marwick TH. Assessment of diastolic function: what the general cardiologist needs to know. Heart. 2005 May;91(5):681-695.
12. Leonardi B, Margossian R, Colan SD, Powell AJ. Relationship of magnetic resonance imaging estimation of myocardial iron to left ventricular systolic and diastolic function in thalassemia. JACC Cardiovasc Imaging. 2008 Sep;1(5):572-578.
13. Yu CM, Sanderson JE, Marwick TH, Oh JK. Tissue Doppler imaging a new prognosticator for cardiovascular diseases. J Am Coll Cardiol. 2007 May 15;49(19):1903-1914.
14. Iarussi D, Di Salvo G, Pergola V, Coppolino P, Tedesco MA, Ratti G, Esposito L, Calabrò R, Ferrara M.. Pulsed doppler tissue imaging and myocardial function in thalassemia major. Heart Vessels. 2003 Mar;18(1):1-6.
15. Daniels LB, Maisel AS.Natriuretic Peptides. J Am Coll Cardiol. 2007 Dec 18;50(25):2357-2368.
16. Ommen SR1, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ.. Clinical utility of Doppler echocardiography and Tissue Doppler imaging in theestimation of left ventricular filling pressures: a comparative simultaneous Doppler-catheterization study. Circulation. 2000 Oct 10;102(15):1788-1794.
17.Sagnella GA. Measurement and importance of plasma brainnatriuretic peptide and related peptides. Ann Clin Biochem. 2001 Mar;38(Pt 2):83-93.
18. Kremastinos DT, Tsiapras DP, Kostopoulou AG, Hamodraka ES, Chaidaroglou AS, Kapsali ED. NT-proBNP levels and diastolic dysfunction in ?-thalassaemia major patients. Eur J Heart Fail. 2007 May;9(5):531-536.
19. Teichholz LE, Kreulen T, Herman MV, Gorlin R.Problems in
echocardiographic volume determinations: Echocardiographic -angiographic
correlations in the presence or absence of asynergy. Am J Cardiol. 1976 Jan;37(1):7-11.
20. Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG; American Society of Echocardiography. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc
Echocardiogr. 2007;20:1021–1041.
21 . Kremastinos DT, Tsiapras DP, Tsetsos GA, Rentoukas EI, Vretou HP, Toutouzas PK. Left ventricular diastolic Doppler characteristics in beta-thalassemia major. Circulation. 1993 Sep;88(3):1127-1135.
22. Vogel M, Anderson LJ, Holden S, Deanfield JE, Pennell DJ, Walker JM. Tissue doppler echocardiography in patients with beta thalassemia detects early myocardial dysfunction related to myocardial iron overload. Eur Heart J. 2003 Jan;24(1):113-119.
23. Kremastinos DT, Toutouzas PK, Vyssoulis GP, Venetis CA, Vretou HP, Avgoustakis DG. Global and segmental left ventricular function in beta-thalassemia. Cardiology. 1985;72(3):129-139.
24.Aypar E1, Alehan D, Hazirolan T, Gümrük F.The efficacy of tissue Doppler imaging in predicting myocardial iron load in patients with beta-thalassemia major: correlation with T2* cardiovascular magnetic resonance.
Int J Cardiovasc Imaging. 2010 Apr;26(4):413-429.
25. Uçar T, Ileri T, Atalay S, Uysal Z, Tutar E, Ertem M.Early detection of myocardial dysfunction in children with beta-thalassaemia major. Int J Cardiovasc Imaging. 2009 Apr;25(4):379-386.
26. Ehlers KH, Levin AR, Markenson AL, Marcus JR, Klein AA,
Hilgartner MW, Engle MA (1980) Longitudinal study of cardiac function in thalassemia major. Ann N Y Acad Sci. 1980;344:397-404.
27.Kremastinos DT, Hamodraka E, Parissis J, Tsiapras D, Dima K, Maisel A. Predictive value of B-type natriuretic peptides in detecting latent left ventricular diastolic dysfunction in beta-thalassemia major. Am Heart J. 2010 Jan;159(1):68-74.
28.Parale GP, Pawar SS, Tapare VS. Assessment of LV diastolic function in patients with beta-thalassemia major with special reference to E/Eann ratio.
J Pediatr Hematol Oncol. 2009 Jan;31(1):69-73.
29.Abdelmoktader AM, Azer HY .Usefulness of pulsed wave tissue doppler imaging in assessment of left ventricular functions in children with beta-thalassemia major.
Indian J Pediatr. 2013 Sep;80(9):721-725.
30.Noori NM, Mehralizadeh S. Echocardiographic evaluation of systolic and diastolic heart function in patients suffering from beta-thalassemia major aged 5-10 years at the Zahedan Research Center for Children and Adolescent Health. Anadolu Kardiyol Derg. 2010 Apr;10(2):150-153.
31. Nishimura RA, Tajik AJ. Evaluation of diastolic filling of left ventricle in health
and disease: Doppler echocardiography is the clinician’s Rosetta Stone. J Am Coll Cardiol. 1997 Jul;30(1):8-18.
32.Agha HM, Beshlawy A, Hamdy M, Sobeih A, El Zahrae F, Abd El Satar IA, AbdelMassih A, Said F, Abd El Aziz O, El Tagui M, Pennell DJ. Early detection of right ventricular diastolic dysfunction by pulsed tissue Doppler echocardiography in iron loaded beta thalassemia patients. Pediatr Cardiol. 2015 Mar;36(3):468-474.
33. Seliem MA, Al-Saad HI, Bou-Holaigah IH, Khan MN, Palileo MR. Left ventricular diastolic dysfunction in congenital chronic anaemias during childhood as determined by comprehensive echocardiographic imaging including acoustic quantification.. Eur J Echocardiogr. 2002 Jun;3(2):103-110.
34. Garadah T, Kassab S, Mahdi N, Abu-Taleb A and Jamsheer A. Pulsed and Tissue Doppler Echocardiographic Changes in Patients with Thalassemia Major Clinical Medicine Insights: Cardiology 2010;3 :1–8.
35. Vaccari M, Crepaz R, Fortini M, Gamberini MR, Scarcia S, Pitscheider W, Bosi G. Left ventricular remodeling, systolic function, and diastolic function in young adults with beta thalassemia intermedia. Chest. 2002 Feb;121(2):506-512.
36. Fitchett DH, Coltart DJ, Littler WA, Leyland MJ, Trueman T, Gozzard DI, Peters TJ. Cardiac involvement in secondary haemochromatosis: a catheter biopsy study and analysis of myocardium. Cardiovasc Res. 1980 Dec;14(12):719-724.
37. Lattanzi F, Bellotti P, Picano E, Chiarella F, Mazzarisi A, Melevendi C, Forni G, Landini L, Distante A, Vecchio C. Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload. Circulation. 1993 Mar;87(3):748-754.
38. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, Lee MM, Park YB, Choi YS, Seo JD, Lee YW.Assessment of mitral annulus velocity by Doppler tissue
imaging in evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997 Aug;30(2):474-480.
39. Gharzuddine WS1, Kazma HK, Nuwayhid IA, Bitar FF, Koussa SF, Moukarbel GV, Taher AT. Doppler characterization of left ventricular diastolic function in beta-thalassaemia major. Evidence for an early stage of impaired relaxation. Eur J Echocardiogr. 2002 Mar;3(1):47-51.
40. Nagueh SF, Lakkis NM, Middleton KJ, Spencer WH 3rd, Zoghbi WA, Quiñones MA. Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy. Circulation. 1999 Jan 19;99(2):254-261.
41. Chrysohoou C, Greenberg M, Pitsavos C, Panagiotakos DB, Ladis V, Barbetseas J, Brili S, Singh S, Stefanadis C.. Diastolic function in young patients with beta- thalassemia major: an echocardiographic study. Echocardiography. 2006 Jan;23(1):38-44.
42.Nikolidakis S, Flessa C, Nikolaou N, Gotsis ED, Koutouzis M, Polyhronaki E, Vrettou E, Kyriakides ZS. Brain natriuretic peptide as marker of myocardial iron load in beta-thalassemia.Int J Cardiol. 2007 Jun 12;118(3):408-409.
43.Lo L, Singer ST . Thalassemia ; current approach to an old disease . Pediatr Clin North Am. 2002 Dec;49(6):1165-91, v.
44. Anderson LJ1, Holden S, Davis B, Prescott E, Charrier CC, Bunce NH, Firmin DN, Wonke B, Porter J, Walker JM, Pennell DJ. Cardiovascular T2 star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. Eur Heart J. 2001 Dec;22(23):2171-2179.
45. Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, Hoffman TM, Kiernan MS, Lerakis S, Piga A, Porter JB, Walker JM, Wood J; American Heart Association Committee on Heart Failure and Transplantation of the Council on Clinical Cardiology and Council on Cardiovascular Radiology and Imaging. Cardiovascular function and treatment in b-Thalassemia major: a consensus statement from the american heart association. Circulation. 2013 Jul 16;128(3):281-308.