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Aortic tortuosity in Turner syndrome is associated with larger ascending aorta

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Abstract

Turner syndrome (TS) is associated with aortic coarctation, dissection and dilation/aneurysm. Predictors of dissection are not well delineated, making decisions regarding prophylactic root replacement challenging. In other disorders, arterial tortuosity is an imaging biomarker associated with increased risk for aortic dissection and adverse cardiovascular events. We aimed to determine if, in TS, arterial tortuosity was associated with aortic dilation or aortic events. We performed a retrospective cohort analysis of unselected women and children with TS who underwent cardiovascular magnetic resonance angiography (MRA) for a prior prospective study. We calculated tortuosity indices including vertebral artery tortuosity index, aortic arch tortuosity index, thoracic aortic tortuosity index (ATI-D), and aortic tortuosity index to the celiac artery (ATI-C). We compared tortuosity in TS patients against age and gender matched controls. We evaluated univariable and multivariable associations between the tortuosity indices and aortic root and ascending aorta size as defined by z-scores, which give a sense of how far a measurement deviates from the mean. We also studied associations between tortuosity and need for aortic root replacement or aortic dissection. Of 184 subjects, with median age 34 years, mean general aortic root z-score was 0.1 ± 1.2 and mean general ascending aortic z-score was 0.4 ± 1.5. Three patients had aortic dissection, and one had prophylactic root replacement, which all occurred prior to first MRA. Vertebral tortuosity index, ATI-D, and ATI-C all increased with age (p < 0.0001) for all. ATI-C was associated with larger general ascending z-score. In multivariable analysis, ATI-C remained independently associated with larger ascending aortic z-scores. The relationship between aortic indices and surgery/dissection could not be evaluated since all were collected post-surgery/dissection. Thoracic aortic tortuosity as measured by ATI-C is independently associated with larger ascending aortic dimensions. In this population with only three aortic dissections occurring prior to imaging assessment, we could not assess for associations between aortic tortuosity and dissection. Studies including more patients with aortic dissection are needed to draw further conclusions.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

TS:

Turner syndrome

MRA:

Magnetic resonance angiography

ATI-D:

Thoracic aortic tortuosity index

ATI-C:

Aortic tortuosity index to the celiac artery

ASI:

Aortic size index

References

  1. Clement-Jones M, Schiller S, Rao E, Blaschke RJ, Zuniga A, Zeller R et al (2000) The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet 9(5):695–702

    Article  CAS  PubMed  Google Scholar 

  2. Olivieri LJ, Baba RY, Arai AE, Bandettini WP, Rosing DR, Bakalov V et al (2013) Spectrum of aortic valve abnormalities associated with aortic dilation across age groups in Turner syndrome. Circulation 6:1018–1023

    PubMed  Google Scholar 

  3. Bondy C, Bakalov VK, Cheng C et al (2013) Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome. J Med Genet 50:662–665

    Article  PubMed  Google Scholar 

  4. Ho VB, Bakalov VK, Cooley M, Van PL, Hood MN, Burklow TR et al (2004) Major vascular anomalies in Turner syndrome: prevalence and magnetic resonance angiographic features. Circulation 110(12):1694–1700

    Article  PubMed  Google Scholar 

  5. Matura L, Ho VB, Rosing DR, Bondy CA (2007) Aortic dilation and dissection in Turner syndrome. Circulation 116:1663–1670

    Article  PubMed  Google Scholar 

  6. Frischhertz BP, Shamszad P, Pedroza C, Milewicz DM, Morris SA (2015) Thoracic aortic dissection and rupture in conotruncal cardiac defects: a population-based study. Int J Cardiol 184:521–527

    Article  PubMed  Google Scholar 

  7. Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME et al (2017) Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 177(3):G1–G70

    Article  CAS  PubMed  Google Scholar 

  8. Shamszad P, Barnes JN, Morris SA (2014) Aortic dissection in hospitalized children and young adults: a multiinstitutional study. Congenit Heart Dis 9:54–62. https://doi.org/10.1111/chd.12090

    Article  PubMed  Google Scholar 

  9. Prakash A, Adlakha H, Rabideau N, Hass CJ, Morris SA, Geva T et al (2015) Segmental aortic stiffness in children and young adults with connective tissue disorders: relationships with age, aortic size, rate of dilation, and surgical root replacement. Circulation 132:595–602

    Article  CAS  PubMed  Google Scholar 

  10. Carlson M, Silberbach M (2007) Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature. J Med Genet 44(12):745–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Carlson M, Airhart N, Lopez L, Silberbach M (2012) Moderate aortic enlargement and bicuspid aortic valve are associated with aortic dissection in Turner syndrome: report of the international turner syndrome aortic dissection registry. Circulation 126(18):2220–2226

    Article  PubMed  Google Scholar 

  12. Morris SA, Orbach DB, Geva T, Singh MN, Gauvreau K, Lacro RV (2011) Increased vertebral artery tortuosity index is associated with adverse outcomes in children and young adults with connective tissue disorders. Circulation 124:388–396. https://doi.org/10.1161/CIRCULATIONAHA.110.990549

    Article  PubMed  Google Scholar 

  13. Franken R, El Morabit A, De Waard V, Timmermans J, Scholte AJ, Van Den Berg MP et al (2015) Increased aortic tortuosity indicates a more severe aortic phenotype in adults with Marfan syndrome. Int J Cardiol 194:7–12

    Article  PubMed  Google Scholar 

  14. Chu LC, Haroun RR, Beaulieu RJ, Black JH, Dietz HC, Fishman EK (2018) Carotid artery tortuosity index is associated with the need for early aortic root replacement in patients with Loeys-Dietz syndrome. J Comput Assist Tomogr 42(5):747–753

    Article  PubMed  Google Scholar 

  15. Morris SA, Payne WA, Lacro RV, Maskatia SA, Masand P, Noel CV et al (2014) Vertebral artery tortuosity in Turner syndrome: is tortuosity a component of the aortopathy phenotype? J Cardiovasc Magn Reson 16(Suppl 1):P115

    Article  PubMed Central  Google Scholar 

  16. Giossi A, Mardighian D, Caria F, Poli L, De Giuli V, Costa P et al (2017) Arterial tortuosity in patients with spontaneous cervical artery dissection. Neuroradiology 59:571–575

    Article  PubMed  Google Scholar 

  17. Baumgartner H, Hung J, Bermejo J, Chambers J, Edvardsen T, Goldstein S et al (2017) Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. J Am Soc Echocardiogr 30(4):372–392

    Article  PubMed  Google Scholar 

  18. Campens L, Demulier L, De Groote K, Vandekerckhove K, De Wolf D, Roman MJ et al (2014) Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories. Am J Cardiol 114(6):914–920. https://doi.org/10.1016/j.amjcard.2014.06.024

    Article  PubMed  Google Scholar 

  19. Colan SD (2013) The why and how of Z scores. J Am Soc Echocardiogr 26(1):38–40

    Article  PubMed  Google Scholar 

  20. Quezada E, Lapidus J, Shaughnessy R, Chen Z, Silberbach M (2015) Aortic dimensions in Turner syndrome. Am J Med Genet A 167A(11):2527–2532. https://doi.org/10.1002/ajmg.a.37208

    Article  PubMed  Google Scholar 

  21. Davies RR, Gallo A, Coady MA, Tellides G, Botta DM, Burke B et al (2006) Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms. Ann Thorac Surg 81:169–177

    Article  PubMed  Google Scholar 

  22. Guala A, Teixidó-Tura G, Rodríguez-Palomares J, Ruiz-Muñoz A (2019) Proximal aorta longitudinal strain predicts aortic root dilation rate and aortic events in Marfan syndrome. Eur Heart J 40(25):2047–2055

    Article  PubMed  Google Scholar 

  23. Fuchs MM, Attenhofer JC, Babovic-Vuksanovic D, Connolly HM, Egbe A (2019) Long-term outcomes in patients with Turner syndrome: a 68-year follow-up. JAMA 8(11):e011501

    Google Scholar 

  24. Duijnhouwer AL, Bons LR, Timmers HJLM, van Kimmenade RRL, Snoeren M (2019) Aortic dilation and outcome in women with Turner syndrome. Heart 105(9):693–700

    Article  PubMed  Google Scholar 

  25. Morris SA (2015) Arterial tortuosity in genetic arteriopathies. Curr Opin Cardiol 30(6):587–593

    Article  PubMed  PubMed Central  Google Scholar 

  26. Humphrey JD, Eberth JF, Dye WW, Gleason RL (2009) Fundamental role of axial stress in compensatory adaptations by arteries. J Biomech 42(1):1–8

    Article  CAS  PubMed  Google Scholar 

  27. Ciurica S, Lopez-Sublet M, Loeys B, Radhouani I, Natarajan N, Vikkula M et al (2019) Arterial tortuosity: novel implications for an old phenotype. Hypertension 73:951–960

    Article  CAS  PubMed  Google Scholar 

  28. Wenn CM, Newman DL (1990) Arterial tortuosity. Australas Phys Eng Sci Med 13(2):67–70

    CAS  PubMed  Google Scholar 

  29. Wu J, Zafar MA, Li Y, Saeyeldin A, Huang Y, Zhao R et al (2019) Ascending aortic length and risk of aortic adverse events. The neglected dimension. J Am Coll Cardiol 74(15):1883–1894

    Article  PubMed  Google Scholar 

  30. Voges I, Jerosch-Herold M, Hedderich J, Pardun E (2012) Normal values of aortic dimensions, distensibility, and pulse wave velocity in children and young adults: a cross-sectional study. J Cardiovasc Magn Reson 14:77

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bondy CA (2006) Growth hormone treatment and aortic dimensions in Turner syndrome. J Clin Endocrinol Metab 91(5):1785–1788

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge Dr. Carolyn Bondy for her role in the original prospective study that generated patient data.

Funding

Research reported in this publication was supported the National Heart, Lung and Blood Institute of the National Institutes of Health under Award Number K23HL127266 (SAM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Division of Cardiology, Department of Pediatrics, New York University Grossman School of Medicine, Hassenfeld Children’s Hospital, New York, USA

    Ranjini Srinivasan

  2. Department of Cardiology, National Heart, Lungs and Blood Institute, Bethesda, USA

    Sujata Shanbhag

  3. Department of Neurology, University of Brescia, Brescia, Italy

    Alessandro Pezzini

  4. Division of Cardiology, Department of Pediatrics, Children’s National Medical Center, Washington DC, USA

    Laura Olivieri

  5. Division of Cardiology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, USA

    Shaine A. Morris

  6. Bethesda, USA

    Ranjini Srinivasan

Authors
  1. Ranjini Srinivasan
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  2. Sujata Shanbhag
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  3. Alessandro Pezzini
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  4. Laura Olivieri
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  5. Shaine A. Morris
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Contributions

RS collected and interpreted the patient data and was a major contributor in writing the manuscript. SS aided in data collection and editing the manuscript. LO collected patient data and edited the manuscript. SM interpreted patient data, performed statistical analysis and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ranjini Srinivasan.

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Conflict of interest

SAM serves as a Scientific Advisor for a clinical trial in Vascular Ehlers-Danlos syndrome and consultant to Aytu Bioscience. The other authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board for the National Heart, Lung and Blood Institute.

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Not applicable.

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Srinivasan, R., Shanbhag, S., Pezzini, A. et al. Aortic tortuosity in Turner syndrome is associated with larger ascending aorta. Int J Cardiovasc Imaging 38, 2479–2490 (2022). https://doi.org/10.1007/s10554-022-02665-1

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  • DOI: https://doi.org/10.1007/s10554-022-02665-1

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