Screening for Familial Thoracic Aortic Aneurysms with Aortic Imaging Does Not Detect All Potential Carriers of the Disease

Abstract

Background: About 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have a first-degree relative with a similar disease. The familial form (FTAAD) of the disease is inherited in an autosomal-dominant pattern. Current guidelines for thoracic aortic disease recommend screening of first-degree relatives of TAAD patients. In known familial disease, screening of both first- and second-degree relatives is recommended. However, the outcomes of such a screening program are unknown.

Methods: We screened all first- and second-degree relatives in seven families with known FTAAD with echocardiography. No underlying gene defect had been detected in these families.

Results: Of 119 persons investigated, 13 had known thoracic aortic disease. In the remaining 106 cases, we diagnosed 19 additional individuals with a dilated ascending thoracic aorta; for an autosomal-dominant disease, the expected number of individuals in this group would have been 40 (p<0.0001). Further, only one of the 20 first-degree relatives younger than 40 years had a dilated aorta, although the expected number of individuals with a disease-causing mutation would have been 10.

Conclusions: In most families with TAAD, a diagnosis still relies on measuring the diameter of the thoracic aorta. We show that a substantial number of previously unknown cases of aortic dilatation can be identified by screening family members. It is, however, not possible to consider anyone free of the condition, even if the aortic diameter is normal, especially at a younger age.

Key Words

Aorta - Aortic aneurysm - Aortic dissection

• References

• 1 Hagan PG, Nienaber CA, Isselbacher EM, Bruckman D, Karavite DJ, Russman PL. , et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA 2000; 283: 897-903 . DOI: 10.1001/jama.283.7.897
• 2 Trimarchi S, Nienaber CA, Rampoldi V, Myrmel T, Suzuki T, Mehta RH. , et al. Contemporary results of surgery in acute type A aortic dissection: The International Registry of Acute Aortic Dissection experience. J Thorac Cardiovasc Surg 2005; 129: 112-22 . DOI: 10.1016/j.jtcvs.2004.09.005
• 3 Olsson C, Hillebrant CG, Liska J, Lockowandt U, Eriksson P, Franco-Cereceda A.. Mortality in acute type A aortic dissection: Validation of the Penn classification. Ann Thorac Surg 2011; 92: 1376-82 . DOI: 10.1016/j.athoracsur.2011.05.011
• 4 Coady MA, Davies RR, Roberts M, Goldstein LJ, Rogalski MJ, Rizzo JA. , et al. Familial patterns of thoracic aortic aneurysms. Arch Surg 1999; 134: 361-7 . DOI: 10.1001/archsurg.134.4.361
• 5 Pomianowski P, Elefteriades JA. The genetics and genomics of thoracic aortic disease. Ann Cardiothorac Surg 2013; 2: 271-9 . DOI: 10.3978/j.issn.2225-319X.2013.05.12
• 6 Gillis E, Van Laer L, Loeys BL. Genetics of thoracic aortic aneurysm: At the crossroad of transforming growth factor-beta signaling and vascular smooth muscle cell contractility. Circ Res 2013; 113: 327-40 . DOI: 10.3978/j.issn.2225-319X.2013.05.12
• 7 Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey Jr. DE. , et al. 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 . DOI: 10.1161/CIR.0b013e3181d4739e
• 8 Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916; 17: 863-71 . DOI: 10.1001/archinte.1916.00080130010002
• 9 Mirea O, Maffessanti F, Gripari P, Tamborini G, Muratori M, Fusini L. , et al. Effects of aging and body size on proximal and ascending aorta and aortic arch: Inner edge-to-inner edge reference values in a large adult population by two-dimensional transthoracic echocardiography. J Am Soc Echocardiogr 2013; 26: 419-27 . DOI: 10.1016/j.echo.2012.12.013
• 10 Davis AE, Lewandowski AJ, Holloway CJ, Ntusi NA, Banerjee R, Nethononda R. , et al. Observational study of regional aortic size referenced to body size: Production of a cardiovascular magnetic resonance nomogram. J Cardiovasc Magn Reson 2014; 16: 9 . DOI: 10.1186/1532-429X-16-9
• 11 Biaggi P, Matthews F, Braun J, Rousson V, Kaufmann PA, Jenni R. Gender, age, and body surface area are the major determinants of ascending aorta dimensions in subjects with apparently normal echocardiograms. J Am Soc Echocardiogr 2009; 22: 720-5 . DOI: 10.1016/j.echo.2009.03.012
• 12 Muraru D, Maffessanti F, Kocabay G, Peluso D, Bianco LD, Piasentini E. , et al. Ascending aorta diameters measured by echocardiography using both leading edge-to-leading edge and inner edge-to-inner edge conventions in healthy volunteers. Eur Heart J Cardiovasc Imaging 2013; 15: 415-422 . DOI: 10.1093/ehjci/jet173
• 13 Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J.. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol 1989; 64: 507-12 . DOI: 10.1016/0002-9149(89)90430-X
• 14 Vasan RS, Larson MG, Benjamin EJ, Levy D.. Echocardiographic reference values for aortic root size: the Framingham Heart Study. J Am Soc Echocardiogr 1995; 8: 793-800 . DOI: 10.1016/S0894-7317(05)80003-3