Prediction of aortic dilation in Turner syndrome - enhancing the use of serial cardiovascular magnetic resonance

Journal of Cardiovascular Magnetic Resonance

Claus H Gravholt³  Niels H Andersen¹  Mogens Erlandsen²  Kristian H Mortensen⁴ 

[1] Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark;Section of Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark;Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Aarhus, Denmark;Department of Radiology, Addenbrooke’s Hospital, Cambridge University Hospitals, Cambridge, United Kingdom

关键词: Bicuspid aortic valve;    Turner syndrome;    Outcomes research;    Cardiovascular magnetic resonance;    Hypertension;    Congenital heart disease;    Follow-up studies;    Aorta;   

Others  :  829209
DOI  :  10.1186/1532-429X-15-47

 received in 2012-10-16, accepted in 2013-05-22,  发布年份 2013

【 摘 要 】

Background

Identification of the subset females with Turner syndrome who face especially high risk of aortic dissection is difficult, and more optimal risk assessment is pivotal in order to improve outcomes. This study aimed to provide comprehensive, dynamic mathematical models of aortic disease in Turner syndrome by use of cardiovascular magnetic resonance (CMR).

Methods

A prospective framework of long-term aortic follow-up was used, which comprised diameters of the thoracic aorta prospectively assessed at nine positions by CMR at the three points in time (baseline [n = 102, age 38 ± 11 years], follow-up [after 2.4 ± 0.4 years, n = 80] and end-of-study [after 4.8 ± 0.5 years, n = 78]). Mathematical models were created that cohesively integrated all measurements at all positions, from all visits and for all participants, and using these models cohesive risk factor analyses were conducted based on which predictive modeling was performed on which predictive modelling was performed.

Results

The cohesive models showed that the variables with effect on aortic diameter were aortic coarctation (P < 0.0001), bicuspid aortic valves (P < 0.0001), age (P < 0.0001), diastolic blood pressure (P = 0.0008), body surface area (P = 0.015) and antihypertensive treatment (P = 0.005). Oestrogen replacement therapy had an effect of borderline significance (P = 0.08). From these data, mathematical models were created that enabled preemption of aortic dilation from CMR derived aortic diameters in scenarios both with and without known risk factors. The fit of the models to the actual data was good.

Conclusion

The presented cohesive model for prediction of aortic diameter in Turner syndrome could help identifying females with rapid growth of aortic diameter, and may enhance clinical decision-making based on serial CMR.

【 授权许可】

   
2013 Mortensen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Mortensen KH, Andersen NH, Gravholt CH. Cardiovascular phenotype in turner syndrome–integrating cardiology, genetics, and endocrinology. Endocr Rev. 2012; 33:667-714.
• [2]Bondy CA. Aortic dissection in turner syndrome. Curr Opin Cardiol. 2008; 23:519-26.
• [3]Bondy CA. Care of girls and women with turner syndrome: a guideline of the turner syndrome study group. J Clin Endocrinol Metab. 2007; 92:10-25.
• [4]Carlson M, Silberbach M. Dissection of the aorta in turner syndrome: two cases and review of 85 cases in the literature. J Med Genet. 2007; 44:745-9.
• [5]Matura LA, Ho VB, Rosing DR, Bondy CA. Aortic dilatation and dissection in turner syndrome. Circulation. 2007; 116:1663-70.
• [6]Hjerrild BE, Mortensen KH, Sorensen KE, Pedersen EM, Andersen NH, Lundorf E, Hansen KW, Horlyck A, Hager A, Christiansen JS, Gravholt CH. Thoracic aortopathy in turner syndrome and the influence of bicuspid aortic valves and blood pressure: a cmr study. J Cardiovasc Magn Reson. 2010; 12:12. BioMed Central Full Text
• [7]Cleemann L, Mortensen KH, Holm K, Smedegaard H, Skouby SO, Wieslander SB, Leffers AM, Leth-Espensen P, Pedersen EM, Gravholt CH. Aortic dimensions in girls and young women with turner syndrome: a magnetic resonance imaging study. Pediatr Cardiol. 2010; 31:497-504.
• [8]Ostberg JE, Brookes JA, McCarthy C, Halcox J, Conway GS. A comparison of echocardiography and magnetic resonance imaging in cardiovascular screening of adults with turner syndrome. J Clin Endocrinol Metab. 2004; 89:5966-71.
• [9]Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM. 2010 accf/aha/aats/acr/asa/sca/scai/sir/sts/svm Guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010; 121:e266-369.
• [10]Mortensen KH, Hjerrild BE, Andersen NH, Sorensen KE, Horlyck A, Pedersen EM, Lundorf E, Christiansen JS, Gravholt CH. Abnormalities of the major intrathoracic arteries in turner syndrome as revealed by magnetic resonance imaging. Cardiol Young. 2010; 20:191-200.
• [11]Mortensen KH, Hjerrild BE, Stochholm K, Andersen NH, Sorensen KE, Lundorf E, Horlyck A, Pedersen EM, Christiansen JS, Gravholt CH. Dilation of the ascending aorta in turner syndrome - a prospective cardiovascular magnetic resonance study. J Cardiovasc Magn Reson. 2011; 13:24. BioMed Central Full Text
• [12]Sorensen TS, Beerbaum P, Korperich H, Pedersen EM. Three-dimensional, isotropic mri: A unified approach to quantification and visualization in congenital heart disease. Int J Cardiovasc Imaging. 2005; 21:283-92.
• [13]Thiebaut R, Jacqmin-Gadda H, Chene G, Leport C, Commenges D. Bivariate linear mixed models using sas proc mixed. Comput Methods Programs Biomed. 2002; 69:249-56.
• [14]SAS/STAT®. 9.1 User’s Guide. Cary, North Carolina, USA: SAS Institute Inc; 2004.
• [15]Harvey AC. Forecasting, structural time series models and the kalman filter. Cambridge, UK: Cambridge University Press; 1989.
• [16]SAS/IML®. 9.1 User’s Guide. Cary, North Carolina, USA: SAS Institute Inc; 2004.
• [17]Zhang YH, Ghodrati A, Brooks DH. An analytical comparison of three spatio-temporal regularization methods for dynamic linear inverse problems in a common statistical framework. Inverse Problems. 2005; 21:357-82.
• [18]Gravholt CH, Hansen KW, Erlandsen M, Ebbehoj E, Christiansen JS. Nocturnal hypertension and impaired sympathovagal tone in turner syndrome. J Hypertens. 2006; 24:353-60.
• [19]Landin-Wilhelmsen K, Bryman I, Wilhelmsen L. Cardiac malformations and hypertension, but not metabolic risk factors, are common in turner syndrome. J Clin Endocrinol Metab. 2001; 86:4166-70.
• [20]Elsheikh M, Casadei B, Conway GS, Wass JA. Hypertension is a major risk factor for aortic root dilatation in women with turner's syndrome. Clin Endocrinol (Oxf). 2001; 54:69-73.
• [21]Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an at1 antagonist, prevents aortic aneurysm in a mouse model of marfan syndrome. Science. 2006; 312:117-21.
• [22]Humphrey JD. Mechanisms of arterial remodeling in hypertension: Coupled roles of wall shear and intramural stress. Hypertension. 2008; 52:195-200.
• [23]Gravholt CH, Hjerrild BE, Mosekilde L, Hansen TK, Rasmussen LM, Frystyk J, Flyvbjerg A, Christiansen JS. Body composition is distinctly altered in turner syndrome: Relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules. Eur J Endocrinol. 2006; 155:583-92.
• [24]Ho VB, Bakalov VK, Cooley M, Van PL, Hood MN, Burklow TR, Bondy CA. Major vascular anomalies in turner syndrome: Prevalence and magnetic resonance angiographic features. Circulation. 2004; 110:1694-700.
• [25]Lanzarini L, Larizza D, Prete G, Calcaterra V, Klersy C. Prospective evaluation of aortic dimensions in turner syndrome: A 2-dimensional echocardiographic study. J Am Soc Echocardiogr. 2007; 20:307-13.
• [26]Burman ED, Keegan J, Kilner PJ. Aortic root measurement by cardiovascular magnetic resonance: specification of planes and lines of measurement and corresponding normal values. Circ Cardiovasc Imaging. 2008; 1:104-13.
• [27]Davies RR, Kaple RK, Mandapati D, Gallo A, Botta DM, Elefteriades JA, Coady MA. Natural history of ascending aortic aneurysms in the setting of an unreplaced bicuspid aortic valve. Ann Thorac Surg. 2007; 83:1338-44.
• [28]Gravholt CH, Landin-Wilhelmsen K, Stochholm K, Hjerrild BE, Ledet T, Djurhuus CB, Sylven L, Baandrup U, Kristensen BO, Christiansen JS. Clinical and epidemiological description of aortic dissection in turner's syndrome. Cardiol Young. 2006; 16:430-6.
• [29]Trolle C, Mortensen KH, Hjerrild BE, Cleemann L, Gravholt CH. Clinical care of adult turner syndrome--new aspects. Pediatr Endocrinol Rev. 2012; 9 Suppl 2:739-49.
• [30]Carlson M, Airhart N, Lopez L, Silberbach M. 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. 2012; 126:2220-6.