J Pediatr Genet 2017; 06(04): 222-226
DOI: 10.1055/s-0037-1603193
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Determining Nt-proBNP Levels with Diastolic Dysfunction in Thalassemia Major Patients

Mable Misha Singh
1   Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
,
Ravindra Kumar
2   Department of Genetics, National Institute for Research in Tribal Health, Indian Council of Medical Research, Jabalpur, Madhya Pradesh, India
,
Satyendra Tewari
3   Department of Cardiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
,
Sarita Agarwal
1   Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
› Author Affiliations
Further Information

Publication History

23 February 2017

10 April 2017

Publication Date:
11 May 2017 (online)

Abstract

Beta thalassemia is an autosomal, recessive disorder, characterized by ineffective erythropoiesis. Chronic transfusions and inability of body to eliminate iron lead to an iron overload, thereby causing damage to heart. Natriuretic peptides (NPs) are produced within the heart, which are then released into the circulation in response to ventricular wall stress. We, therefore, aimed to study the relation between ventricular dysfunction and N-terminal pro-B-type natriuretic peptides (NT-proBNPs). We enrolled 105 patients with increased serum ferritin levels and echocardiography was performed. We collected blood samples and NT-proBNP levels were measured in them. Though we found that the studied group had no significant difference in the mean serum NT-proBNP levels, in patients with or without hypertrophy (n = 37, p = 0.992), the NT-proBNP levels were found to be significantly increased in patients with diastolic dysfunction (n = 24, p < 0.0001 with mean values of 577.67 ± 122.01 and 456.50 ± 48.40 pg/mL in patients with and without diastolic dysfunction, respectively). The NT-proBNP levels correlated well with the echocardiography indices, such as left ventricular end-systolic diameter (LVESD), ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/E' ratio), and ratio of the early (E) to late (A) ventricular filling velocities (E/A ratio), and were found to have significant positive correlation with the serum ferritin levels. The NT-proBNP levels correlated significantly with diastolic dysfunction; thus, serum ferritin levels could be useful for assessing the diastolic dysfunction in patients with beta thalassemia.

 
  • References

  • 1 Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis 2010; 5: 11 . Doi: 10.1186/1750-1172-5-11
  • 2 Borgna-Pignatti C, Rugolotto S, De Stefano P. , et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89 (10) 1187-1193
  • 3 Aessopos A, Berdoukas V, Tsironi M. The heart in transfusion dependent homozygous thalassaemia today--prediction, prevention and management. Eur J Haematol 2008; 80 (02) 93-106
  • 4 Bornaun H, Dedeoglu R, Oztarhan K. , et al. Detection of early right ventricular dysfunction in young patients with thalassemia major using tissue Doppler imaging. Iran J Pediatr 2016; 26 (03) e5808 . Doi: 10.5812/ijp.5808
  • 5 Ibrahim MH, Azab AA, Kamal NM. , et al. Early detection of myocardial dysfunction in poorly treated pediatric thalassemia children and adolescents: Two Saudi centers experience. Ann Med Surg (Lond) 2016; 9: 6-11
  • 6 Seino Y, Ogawa A, Yamashita T. , et al. Application of NT-proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure. Eur J Heart Fail 2004; 6 (03) 295-300
  • 7 Mak GS, DeMaria A, Clopton P, Maisel AS. Utility of B-natriuretic peptide in the evaluation of left ventricular diastolic function: comparison with tissue Doppler imaging recordings. Am Heart J 2004; 148 (05) 895-902
  • 8 Kinnunen P, Vuolteenaho O, Ruskoaho H. Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching. Endocrinology 1993; 132 (05) 1961-1970
  • 9 Sagnella GA. Measurement and importance of plasma brain natriuretic peptide and related peptides. Ann Clin Biochem 2001; 38 (Pt 2): 83-93
  • 10 Bruins S, Fokkema MR, Römer JW. , et al. High intraindividual variation of B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure. Clin Chem 2004; 50 (11) 2052-2058
  • 11 Wu AH, Smith A, Wieczorek S. , et al. Biological variation for N-terminal pro- and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure. Am J Cardiol 2003; 92 (05) 628-631
  • 12 Kremastinos DT, Tsiapras DP, Kostopoulou AG, Hamodraka ES, Chaidaroglou AS, Kapsali ED. NT-proBNP levels and diastolic dysfunction in beta-thalassaemia major patients. Eur J Heart Fail 2007; 9 (05) 531-536
  • 13 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; 159 (01) 68-74
  • 14 Ragab SM, Fathy WM, El-Aziz WF, Helal RT. 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. Mediterr J Hematol Infect Dis 2015; 7 (01) e2015051 . Doi: 10.4084/MJHID.2015.051
  • 15 Nagueh SF, Smiseth OA, Appleton CP. , et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2016; 29 (04) 277-314
  • 16 Devereux RB, Alonso DR, Lutas EM. , et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57 (06) 450-458
  • 17 de Simone G, Daniels SR, Devereux RB. , et al. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol 1992; 20 (05) 1251-1260
  • 18 Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009; 22 (06) 709-714
  • 19 Lekawanvijit S, Chattipakorn N. Iron overload thalassemic cardiomyopathy: iron status assessment and mechanisms of mechanical and electrical disturbance due to iron toxicity. Can J Cardiol 2009; 25 (04) 213-218
  • 20 Spirito P, Lupi G, Melevendi C, Vecchio C. Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. Circulation 1990; 82 (01) 88-94
  • 21 Kremastinos DT, Tsetsos GA, Tsiapras DP, Karavolias GK, Ladis VA, Kattamis CA. Heart failure in beta thalassemia: a 5-year follow-up study. Am J Med 2001; 111 (05) 349-354
  • 22 Shimizu H, Masuta K, Aono K. , et al. Molecular forms of human brain natriuretic peptide in plasma. Clin Chim Acta 2002; 316 (1-2): 129-135
  • 23 Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol 2007; 50 (25) 2357-2368
  • 24 van Kimmenade RR, Januzzi Jr JL. Emerging biomarkers in heart failure. Clin Chem 2012; 58 (01) 127-138
  • 25 Mueller T, Gegenhuber A, Poelz W, Haltmayer M. Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure. Heart 2005; 91 (05) 606-612
  • 26 Wang TJ, Larson MG, Levy D. , et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 2004; 350 (07) 655-663
  • 27 Garadah TS, Mahdi N, Kassab S, Shoroqi IA, Abu-Taleb A, Jamsheer A. The pro-BNP serum level and echocardiographic tissue Doppler abnormalities in patients with beta thalassemia major. Clin Med Insights Cardiol 2010; 4: 135-141
  • 28 Alizadeh B, Badiee Z, Mahmoudi M, Mohajery M. Evaluating the correlation between serum NT-proBNP level and diastolic dysfunction severity in beta-thalassemia major patients. J Tehran Heart Cent 2016; 11 (02) 68-72
  • 29 Nikolidakis S, Flessa C, Nikolaou N. , et al. Brain natriuretic peptide as marker of myocardial iron load in beta-thalassemia. Int J Cardiol 2007; 118 (03) 408-409
  • 30 Delaporta P, Kattamis A, Apostolakou F. , et al. Correlation of NT-proBNP levels and cardiac iron concentration in patients with transfusion-dependent thalassemia major. Blood Cells Mol Dis 2013; 50 (01) 20-24
  • 31 Dokainish H, Zoghbi WA, Lakkis NM. , et al. Optimal noninvasive assessment of left ventricular filling pressures: a comparison of tissue Doppler echocardiography and B-type natriuretic peptide in patients with pulmonary artery catheters. Circulation 2004; 109 (20) 2432-2439
  • 32 Troughton RW, Prior DL, Pereira JJ. , et al. Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function. J Am Coll Cardiol 2004; 43 (03) 416-422
  • 33 Tschöpe C, Kasner M, Westermann D, Gaub R, Poller WC, Schultheiss HP. The role of NT-proBNP in the diagnostics of isolated diastolic dysfunction: correlation with echocardiographic and invasive measurements. Eur Heart J 2005; 26 (21) 2277-2284
  • 34 Mehrzad V, Khajouei AS, Fahami E. Correlation of N-terminal pro-B-type natriuretic peptide levels and cardiac magnetic resonance imaging T2* in patients with β-thalassaemia major. Blood Transfus 2016; 14 (06) 516-520