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Abnormalities in aortic properties: a potential link between left ventricular diastolic function and ventricular—aortic coupling in sickle cell disease

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Abstract

Left ventricular (LV) diastolic dysfunction in patients with sickle cell disease (SCD) is associated with increased mortality. However, its mechanisms are not well known, preventing the development of effective therapies. We hypothesized that patients with SCD have altered aortic properties despite normal blood pressure, which may contribute towards the development of diastolic dysfunction. We studied 31 stable adult patients with SCD (32 ± 7 years) and 12 healthy controls of similar age (29 ± 10 years) who underwent echocardiography and cardiovascular magnetic resonance (CMR) imaging on the same day. Echocardiographic measurements of mitral inflow and mitral annulus velocities were used to evaluate LV diastolic function. CMR imaging included standard LV function evaluation and myocardial tissue characterization as well as velocity-encoded images of the ascending aorta to measure aortic diastolic cross-sectional area, distensibility, as well as peaks and volumes of the global, forward and backward blood flow rate. Compared to controls, SCD patients had increased aortic diastolic area, global stroke volume, and both forward and backward flow, while aortic distensibility and peripheral blood pressure were similar. Furthermore, peak backward flow rate and volume were able to discriminate between patients with and without diastolic dysfunction. Our findings show that some aortic properties are altered in SCD patients and may be associated with diastolic dysfunction despite normal systolic blood pressure. If confirmed in larger studies, these aortic changes could be a novel therapeutic target to prevent or delay the development of LV diastolic dysfunction in SCD and thus potentially improve outcomes in these patients.

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References

  1. Rees DC, Williams TN, Gladwin MT (2010) Sickle-cell disease. Lancet 376:2018–2031

    Article  CAS  PubMed  Google Scholar 

  2. Acar P, Maunoury C, de Montalembert M, Dulac Y (2003) [Abnormalities of myocardial perfusion in sickle cell disease in childhood: a study of myocardial scintigraphy]. Arch Mal Coeur Vaiss 96:507–510

    CAS  PubMed  Google Scholar 

  3. Sutton LL, Castro O, Cross DJ, Spencer JE, Lewis JF (1994) Pulmonary hypertension in sickle cell disease. Am J Cardiol 74:626–628

    Article  CAS  PubMed  Google Scholar 

  4. Aessopos A, Farmakis D, Tsironi M, Diamanti-Kandarakis E, Matzourani M, Fragodimiri C, Hatziliami A, Karagiorga M (2007) Endothelial function and arterial stiffness in sickle-thalassemia patients. Atherosclerosis 191:427–432

    Article  CAS  PubMed  Google Scholar 

  5. Gerry JL, Baird MG, Fortuin NJ (1976) Evaluation of left ventricular function in patients with sickle cell anemia. Am J Med 60:968–972

    Article  CAS  PubMed  Google Scholar 

  6. Şan M, Demirtaş M, Burgut R, Birand A, Başlamişh F (1998) Left ventricular systolic and diastolic functions in patients with sickle cell anemia. Int J Angiol Off Publ Int Coll Angiol Inc 7:185–187

    Google Scholar 

  7. Westwood MA, Shah F, Anderson LJ, Strange JW, Tanner MA, Maceira AM, Howard J, Porter JB, Walker JM, Wonke B, Pennell DJ (2007) Myocardial tissue characterization and the role of chronic anemia in sickle cell cardiomyopathy. J Magn Reson Imaging JMRI 26:564–568

    Article  PubMed  Google Scholar 

  8. Junqueira FP, Fernandes JL, Cunha GM, Kubo TTA, Lima CMAO, Lima DBP, Uellendhal M, Sales SR, Cunha CAS, de Pessoa VLR, Lobo CLC, Marchiori E (2013) Right and left ventricular function and myocardial scarring in adult patients with sickle cell disease: a comprehensive magnetic resonance assessment of hepatic and myocardial iron overload. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson 15:83

    Google Scholar 

  9. Cheung YF, Chan GCF, Ha SY (2002) Arterial stiffness and endothelial function in patients with beta-thalassemia major. Circulation 106:2561–2566

    Article  CAS  PubMed  Google Scholar 

  10. Barbosa MM, Vasconcelos MCM, Ferrari TCA, Fernandes BM, Passaglia LG, Silva CM, Nunes MCP (2014) Assessment of ventricular function in adults with sickle cell disease: role of two-dimensional speckle-tracking strain. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 27:1216–1222

    Article  Google Scholar 

  11. Hammoudi N, Arangalage D, Djebbar M, Stojanovic KS, Charbonnier M, Isnard R, Girot R, Michel P-L, Lionnet F (2014) Subclinical left ventricular systolic impairment in steady state young adult patients with sickle-cell anemia. Int J Cardiovasc Imaging 30:1297–1304

    Article  PubMed  Google Scholar 

  12. Ahmad H, Gayat E, Yodwut C, Abduch MC, Patel AR, Weinert L, Desai A, Tsang W, Garcia JGN, Lang RM, Mor-Avi V (2012) Evaluation of myocardial deformation in patients with sickle cell disease and preserved ejection fraction using three-dimensional speckle tracking echocardiography. Echocardiography 29:962–969

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fitzhugh CD, Lauder N, Jonassaint JC, Telen MJ, Zhao X, Wright EC, Gilliam FR, De Castro LM (2010) Cardiopulmonary complications leading to premature deaths in adult patients with sickle cell disease. Am J Hematol 85:36–40

    PubMed  Google Scholar 

  14. Sachdev V, Machado RF, Shizukuda Y, Rao YN, Sidenko S, Ernst I, St Peter M, Coles WA, Rosing DR, Blackwelder WC, Castro O, Kato GJ, Gladwin MT (2007) Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease. J Am Coll Cardiol 49:472–479

    Article  PubMed  PubMed Central  Google Scholar 

  15. Desai AA, Patel AR, Ahmad H, Groth JV, Thiruvoipati T, Turner K, Yodwut C, Czobor P, Artz N, Machado RF, Garcia JGN, Lang RM (2014) Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy. Circ Cardiovasc Imaging 7:430–437

    Article  PubMed  PubMed Central  Google Scholar 

  16. Varat MA, Adolph RJ, Fowler NO (1972) Cardiovascular effects of anemia. Am Heart J 83:415–426

    Article  CAS  PubMed  Google Scholar 

  17. Denenberg BS, Criner G, Jones R, Spann JF (1983) Cardiac function in sickle cell anemia. Am J Cardiol 51:1674–1678

    Article  CAS  PubMed  Google Scholar 

  18. Voskaridou E, Christoulas D, Terpos E (2012) Sickle-cell disease and the heart: review of the current literature. Br J Haematol 157:664–673

    Article  CAS  PubMed  Google Scholar 

  19. Hatch FE, Crowe LR, Miles DE, Young JP, Portner ME (1989) Altered vascular reactivity in sickle hemoglobinopathy. A possible protective factor from hypertension. Am J Hypertens 2:2–8

    Article  CAS  PubMed  Google Scholar 

  20. Belhassen L, Pelle G, Sediame S, Bachir D, Carville C, Bucherer C, Lacombe C, Galacteros F, Adnot S (2001) Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation. Blood 97:1584–1589

    Article  CAS  PubMed  Google Scholar 

  21. Eberhardt RT, McMahon L, Duffy SJ, Steinberg MH, Perrine SP, Loscalzo J, Coffman JD, Vita JA (2003) Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol 74:104–111

    Article  CAS  PubMed  Google Scholar 

  22. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt J-U (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 28(1–39):e14

    Google Scholar 

  23. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr J Work Group Echocardiogr Eur Soc Cardiol. 10:165–193

    Article  Google Scholar 

  24. Lorenz CH, Walker ES, Morgan VL, Klein SS, Graham TP (1999) Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson 1:7–21

    CAS  Google Scholar 

  25. Herment A, Kachenoura N, Lefort M, Bensalah M, Dogui A, Frouin F, Mousseaux E, De Cesare A (2010) Automated segmentation of the aorta from phase contrast MR images: validation against expert tracing in healthy volunteers and in patients with a dilated aorta. J Magn Reson Imaging JMRI 31:881–888

    Article  PubMed  Google Scholar 

  26. Dogui A, Kachenoura N, Frouin F, Lefort M, De Cesare A, Mousseaux E, Herment A (2011) Consistency of aortic distensibility and pulse wave velocity estimates with respect to the Bramwell-Hill theoretical model: a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson Off J Soc Cardiovasc Magn Reson 13:11

    Google Scholar 

  27. Bensalah MZ, Bollache E, Kachenoura N, Giron A, De Cesare A, Macron L, Lefort M, Redheuill A, Mousseaux E (2014) Geometry is a major determinant of flow reversal in proximal aorta. Am J Physiol Heart Circ Physiol 306:H1408–H1416

    Article  CAS  PubMed  Google Scholar 

  28. Gladwin MT, Sachdev V (2012) Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol 59:1123–1133

    Article  PubMed  Google Scholar 

  29. Covitz W, Espeland M, Gallagher D, Hellenbrand W, Leff S, Talner N (1995) The heart in sickle cell anemia. The cooperative study of sickle cell disease (CSSCD). Chest 108:1214–1219

    Article  CAS  PubMed  Google Scholar 

  30. Lemogoum D, Van Bortel L, Najem B, Dzudie A, Teutcha C, Madu E, Leeman M, Degaute J-P, van de Borne P (2004) Arterial stiffness and wave reflections in patients with sickle cell disease. Hypertension 44:924–929

    Article  CAS  PubMed  Google Scholar 

  31. Belizna C, Loufrani L, Ghali A, Lahary A, Primard E, Louvel J-P, Henrion D, Lévesque H, Ifrah N (2012) Arterial stiffness and stroke in sickle cell disease. Stroke J Cereb Circ 43:1129–1130

    Article  Google Scholar 

  32. Latham RD, Westerhof N, Sipkema P, Rubal BJ, Reuderink P, Murgo JP (1985) Regional wave travel and reflections along the human aorta: a study with six simultaneous micromanometric pressures. Circulation 72:1257–1269

    Article  CAS  PubMed  Google Scholar 

  33. Bogren HG, Klipstein RH, Firmin DN, Mohiaddin RH, Underwood SR, Rees RS, Longmore DB (1989) Quantitation of antegrade and retrograde blood flow in the human aorta by magnetic resonance velocity mapping. Am Heart J 117:1214–1222

    Article  CAS  PubMed  Google Scholar 

  34. Hope TA, Markl M, Wigström L, Alley MT, Miller DC, Herfkens RJ (2007) Comparison of flow patterns in ascending aortic aneurysms and volunteers using four-dimensional magnetic resonance velocity mapping. J Magn Reson Imaging JMRI 26:1471–1479

    Article  PubMed  Google Scholar 

  35. Bogren HG, Mohiaddin RH, Klipstein RK, Firmin DN, Underwood RS, Rees SR, Longmore DB (1989) The function of the aorta in ischemic heart disease: a magnetic resonance and angiographic study of aortic compliance and blood flow patterns. Am Heart J 118:234–247

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Victor Mor-Avi.

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Bollache, E., Kachenoura, N., Lang, R.M. et al. Abnormalities in aortic properties: a potential link between left ventricular diastolic function and ventricular—aortic coupling in sickle cell disease. Int J Cardiovasc Imaging 32, 965–973 (2016). https://doi.org/10.1007/s10554-016-0863-7

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  • DOI: https://doi.org/10.1007/s10554-016-0863-7

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