Epidemiology, risk factors, pathogenesis and natural history of thoracic aortic aneurysm
- Y Joseph Woo, MD
Y Joseph Woo, MD
- Department Chair, Cardiothoracic Surgery
- Stanford University
- Emile R Mohler III, MD
Emile R Mohler III, MD
- Section Editor — Vascular Medicine
- Professor of Medicine
- University of Pennsylvania School of Medicine
- James H Black, III, MD
James H Black, III, MD
- Associate Professor of Surgery
- Johns Hopkins University
- Christina L Greene, MD
Christina L Greene, MD
- Cardiothoracic Surgery Resident
- Stanford University
- Section Editors
- James Hoekstra, MD
James Hoekstra, MD
- Section Editor — Adult Cardiology Emergencies
- Professor and Fredrick Glass Chair
- Wake Forest University
- John F Eidt, MD
John F Eidt, MD
- Section Editor — Vascular and Endovascular Surgery
- Professor of Surgery, Texas A&M Health Sciences Center - Dallas Campus
- Vice Chair of Vascular Surgical Services, Baylor Heart and Vascular Hospital at Dallas
- Joseph L Mills, Sr, MD
Joseph L Mills, Sr, MD
- Section Editor — Vascular and Endovascular Surgery
- Professor and Chief
- Division of Vascular Surgery and Endovascular Therapy
- Baylor College of Medicine
- Heidi M Connolly, MD, FASE
Heidi M Connolly, MD, FASE
- Section Editor — Congenital Heart Disease
- Professor of Medicine
- Mayo Medical School
It is important to have a working knowledge of the risk factors, pathophysiology, and natural history of thoracic aortic aneurysm (TAA) to aid with clinical decision making. Most thoracic aortic aneurysms (TAAs) identified in patients over age 65 years are degenerative and share many of the same risk factors as abdominal aortic aneurysm (AAA); inflammatory disorders such as giant cell arteritis are also associated with TAA, primarily in this age group. TAA identified in patients younger than 65 years is more often associated with a genetic predisposition that can be familial or related to defined genetic disorders such as Marfan syndrome. About 25 percent of patients with thoracic aortic aneurysm (TAA) will also be found to have an abdominal aortic aneurysm (AAA) [1-3].
The natural history of TAA is one of slow expansion with a progressive increase in the risk of aortic dissection at larger aortic sizes. The rate of aortic expansion depends upon aneurysm etiology, diameter, and location. Expansion rates for TAA are generally less than those of AAA. In addition, the generally slow expansion of TAA means that most patients with TAA are asymptomatic and many patients will succumb to other disease processes without being aware that TAA is present. Aneurysms that do produce symptoms are typically very large and at risk for rupture, which is associated with high rates of morbidity and mortality.
This topic will review the etiology, risk factors, pathogenesis, and natural history of true thoracic aortic aneurysm. The clinical features, diagnosis and management of thoracic aortic aneurysm, including surgical and endovascular repair, are discussed elsewhere. (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm" and "Management of thoracic aortic aneurysm in adults" and "Overview of open surgical repair of the thoracic aorta" and "Endovascular repair of the thoracic aorta".)
DEFINITION AND CLASSIFICATION
A true aneurysm is defined as a segmental, full-thickness dilation of a blood vessel having at least a 50 percent increase in diameter compared with the expected normal diameter [4-6]. The normal diameter of the thoracic aorta varies with location and age. Normal average diameters are discussed separately. (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm", section on 'Definition of TAA'.)
Pseudoaneurysm (false aneurysm) represents a collection of blood and connective tissue outside the aortic wall, which in the thoracic aorta can result from a contained aortic rupture or from a variety of pathologic processes such as penetrating aortic ulcer, aortic dissection, trauma, or other acute aortic syndromes. These disorders are discussed elsewhere. (See "Overview of acute aortic syndromes" and "Blunt thoracic aortic injury" and "Overview of acute aortic syndromes", section on 'Definition and pathophysiology'.)
- Crawford ES, Cohen ES. Aortic aneurysm: a multifocal disease. Presidential address. Arch Surg 1982; 117:1393.
- Pressler V, McNamara JJ. Aneurysm of the thoracic aorta. Review of 260 cases. J Thorac Cardiovasc Surg 1985; 89:50.
- Bickerstaff LK, Pairolero PC, Hollier LH, et al. Thoracic aortic aneurysms: a population-based study. Surgery 1982; 92:1103.
- Johnston KW, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery. J Vasc Surg 1991; 13:452.
- Hiratzka LF, Bakris GL, Beckman JA, 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.
- Creager MA, Belkin M, Bluth EI, et al. 2012 ACCF/AHA/ACR/SCAI/SIR/STS/SVM/SVN/SVS Key data elements and definitions for peripheral atherosclerotic vascular disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Data Standards (Writing Committee to develop Clinical Data Standards for peripheral atherosclerotic vascular disease). J Am Coll Cardiol 2012; 59:294.
- Itani Y, Watanabe S, Masuda Y, et al. Measurement of aortic diameters and detection of asymptomatic aortic aneurysms in a mass screening program using a mobile helical computed tomography unit. Heart Vessels 2002; 16:42.
- Kälsch H, Lehmann N, Möhlenkamp S, et al. Body-surface adjusted aortic reference diameters for improved identification of patients with thoracic aortic aneurysms: results from the population-based Heinz Nixdorf Recall study. Int J Cardiol 2013; 163:72.
- Clouse WD, Hallett JW Jr, Schaff HV, et al. Improved prognosis of thoracic aortic aneurysms: a population-based study. JAMA 1998; 280:1926.
- Elefteriades JA, Farkas EA. Thoracic aortic aneurysm clinically pertinent controversies and uncertainties. J Am Coll Cardiol 2010; 55:841.
- Olsson C, Thelin S, Ståhle E, et al. Thoracic aortic aneurysm and dissection: increasing prevalence and improved outcomes reported in a nationwide population-based study of more than 14,000 cases from 1987 to 2002. Circulation 2006; 114:2611.
- von Allmen RS, Anjum A, Powell JT. Incidence of descending aortic pathology and evaluation of the impact of thoracic endovascular aortic repair: a population-based study in England and Wales from 1999 to 2010. Eur J Vasc Endovasc Surg 2013; 45:154.
- Acosta S, Ogren M, Bengtsson H, et al. Increasing incidence of ruptured abdominal aortic aneurysm: a population-based study. J Vasc Surg 2006; 44:237.
- Ferro CR, de Oliveira DC, Guerra Fde F, et al. Prevalence and risk factors for combined coronary artery disease and aortic aneurysm. Arq Bras Cardiol 2007; 88:40.
- Booher AM, Eagle KA. Diagnosis and management issues in thoracic aortic aneurysm. Am Heart J 2011; 162:38.
- Coady MA, Davies RR, Roberts M, et al. Familial patterns of thoracic aortic aneurysms. Arch Surg 1999; 134:361.
- Isselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation 2005; 111:816.
- Reed D, Reed C, Stemmermann G, Hayashi T. Are aortic aneurysms caused by atherosclerosis? Circulation 1992; 85:205.
- Tilson MD. Aortic aneurysms and atherosclerosis. Circulation 1992; 85:378.
- Palmieri V, Bella JN, Arnett DK, et al. Aortic root dilatation at sinuses of valsalva and aortic regurgitation in hypertensive and normotensive subjects: The Hypertension Genetic Epidemiology Network Study . Hypertension 2001; 37:1229.
- Prakash SK, Pedroza C, Khalil YA, Milewicz DM. Diabetes and reduced risk for thoracic aortic aneurysms and dissections: a nationwide case-control study. J Am Heart Assoc 2012; 1.
- Agricola E, Slavich M, Tufaro V, et al. Prevalence of thoracic ascending aortic aneurysm in adult patients with known abdominal aortic aneurysm: an echocardiographic study. Int J Cardiol 2013; 168:3147.
- Kuzmik GA, Feldman M, Tranquilli M, et al. Concurrent intracranial and thoracic aortic aneurysms. Am J Cardiol 2010; 105:417.
- Ogata A, Kawashima M, Matsushima T. Behçet's disease with ruptured anterior communicating artery aneurysm following ruptured thoracic aortic aneurysm. Neurol Med Chir (Tokyo) 2013; 53:189.
- Schievink WI, Raissi SS, Maya MM, Velebir A. Screening for intracranial aneurysms in patients with bicuspid aortic valve. Neurology 2010; 74:1430.
- Lee JJ, Dimick JB, Williams DM, et al. Existence of abdominal aortic aneurysms in patients with thoracic aortic dissections. J Vasc Surg 2003; 38:671.
- De León Ayala IA, Chen YF. Acute aortic dissection: an update. Kaohsiung J Med Sci 2012; 28:299.
- Pacini D, Leone O, Turci S, et al. Incidence, etiology, histologic findings, and course of thoracic inflammatory aortopathies. Ann Thorac Surg 2008; 86:1518.
- Nuenninghoff DM, Hunder GG, Christianson TJ, et al. Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years. Arthritis Rheum 2003; 48:3522.
- Evans JM, Bowles CA, Bjornsson J, et al. Thoracic aortic aneurysm and rupture in giant cell arteritis. A descriptive study of 41 cases. Arthritis Rheum 1994; 37:1539.
- Milewicz DM, Michael K, Fisher N, et al. Fibrillin-1 (FBN1) mutations in patients with thoracic aortic aneurysms. Circulation 1996; 94:2708.
- Milewicz DM, Chen H, Park ES, et al. Reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/dissections. Am J Cardiol 1998; 82:474.
- Pannu H, Fadulu VT, Chang J, et al. Mutations in transforming growth factor-beta receptor type II cause familial thoracic aortic aneurysms and dissections. Circulation 2005; 112:513.
- Guo D, Hasham S, Kuang SQ, et al. Familial thoracic aortic aneurysms and dissections: genetic heterogeneity with a major locus mapping to 5q13-14. Circulation 2001; 103:2461.
- Vaughan CJ, Casey M, He J, et al. Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder. Circulation 2001; 103:2469.
- Khau Van Kien P, Mathieu F, Zhu L, et al. Mapping of familial thoracic aortic aneurysm/dissection with patent ductus arteriosus to 16p12.2-p13.13. Circulation 2005; 112:200.
- Judge DP, Dietz HC. Therapy of Marfan syndrome. Annu Rev Med 2008; 59:43.
- Neptune ER, Frischmeyer PA, Arking DE, et al. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat Genet 2003; 33:407.
- Gott VL, Greene PS, Alejo DE, et al. Replacement of the aortic root in patients with Marfan's syndrome. N Engl J Med 1999; 340:1307.
- Adams JN, Trent RJ. Aortic complications of Marfan's syndrome. Lancet 1998; 352:1722.
- Germain DP, Herrera-Guzman Y. Vascular Ehlers-Danlos syndrome. Ann Genet 2004; 47:1.
- http://www.marfan.org/marfan/2290/Loeys-Dietz-Syndrome/ http://www.ncbi.nlm.nih.gov/books/NBK1133/.
- Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med 2006; 355:788.
- Gøtzsche CO, Krag-Olsen B, Nielsen J, et al. Prevalence of cardiovascular malformations and association with karyotypes in Turner's syndrome. Arch Dis Child 1994; 71:433.
- Ostberg JE, Brookes JA, McCarthy C, et al. A comparison of echocardiography and magnetic resonance imaging in cardiovascular screening of adults with Turner syndrome. J Clin Endocrinol Metab 2004; 89:5966.
- Albornoz G, Coady MA, Roberts M, et al. Familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns. Ann Thorac Surg 2006; 82:1400.
- Mongeon FP, Gurvitz MZ, Broberg CS, et al. Aortic root dilatation in adults with surgically repaired tetralogy of fallot: a multicenter cross-sectional study. Circulation 2013; 127:172.
- von Kodolitsch Y, Aydin MA, Koschyk DH, et al. Predictors of aneurysmal formation after surgical correction of aortic coarctation. J Am Coll Cardiol 2002; 39:617.
- 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.
- Kallenbach K. Editorial comment: Moderate aneuryms of the ascending aorta in stenotic bicuspid aortic valve--life threatening or merely an epiphenomenon? Eur J Cardiothorac Surg 2012; 42:838.
- Musunuru K. Transforming growth factor β2 mutations and familial thoracic aortic aneurysms. Circ Cardiovasc Genet 2012; 5:593.
- Glazer NL. Copy number variation contributes to sporadic and familial thoracic aortic aneurysms and dissections. Circ Cardiovasc Genet 2011; 4:212.
- Verma S, Siu SC. Aortic dilatation in patients with bicuspid aortic valve. N Engl J Med 2014; 370:1920.
- Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol 1970; 26:72.
- Cripe L, Andelfinger G, Martin LJ, et al. Bicuspid aortic valve is heritable. J Am Coll Cardiol 2004; 44:138.
- Biner S, Rafique AM, Ray I, et al. Aortopathy is prevalent in relatives of bicuspid aortic valve patients. J Am Coll Cardiol 2009; 53:2288.
- Nistri S, Sorbo MD, Marin M, et al. Aortic root dilatation in young men with normally functioning bicuspid aortic valves. Heart 1999; 82:19.
- Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic valves. JAMA 2011; 306:1104.
- Martens T, Van Herzeele I, De Ryck F, et al. Multiple aneurysms in a patient with aneurysms-osteoarthritis syndrome. Ann Thorac Surg 2013; 95:332.
- van der Linde D, Bekkers JA, Mattace-Raso FU, et al. Progression rate and early surgical experience in the new aggressive aneurysms-osteoarthritis syndrome. Ann Thorac Surg 2013; 95:563.
- van der Linde D, van de Laar IM, Bertoli-Avella AM, et al. Aggressive cardiovascular phenotype of aneurysms-osteoarthritis syndrome caused by pathogenic SMAD3 variants. J Am Coll Cardiol 2012; 60:397.
- Cheung C, Bernardo AS, Trotter MW, et al. Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility. Nat Biotechnol 2012; 30:165.
- Bonderman D, Gharehbaghi-Schnell E, Wollenek G, et al. Mechanisms underlying aortic dilatation in congenital aortic valve malformation. Circulation 1999; 99:2138.
- Tadros TM, Klein MD, Shapira OM. Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. Circulation 2009; 119:880.
- Coady MA, Rizzo JA, Goldstein LJ, Elefteriades JA. Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections. Cardiol Clin 1999; 17:615.
- Campa JS, Greenhalgh RM, Powell JT. Elastin degradation in abdominal aortic aneurysms. Atherosclerosis 1987; 65:13.
- Jackson V, Olsson T, Kurtovic S, et al. Matrix metalloproteinase 14 and 19 expression is associated with thoracic aortic aneurysms. J Thorac Cardiovasc Surg 2012; 144:459.
- Huusko T, Salonurmi T, Taskinen P, et al. Elevated messenger RNA expression and plasma protein levels of osteopontin and matrix metalloproteinase types 2 and 9 in patients with ascending aortic aneurysms. J Thorac Cardiovasc Surg 2013; 145:1117.
- Serra R, Grande R, Montemurro R, et al. The role of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in central and peripheral arterial aneurysms. Surgery 2015; 157:155.
- MacSweeney ST, Powell JT, Greenhalgh RM. Pathogenesis of abdominal aortic aneurysm. Br J Surg 1994; 81:935.
- Allaire E, Hasenstab D, Kenagy RD, et al. Prevention of aneurysm development and rupture by local overexpression of plasminogen activator inhibitor-1. Circulation 1998; 98:249.
- Allaire E, Forough R, Clowes M, et al. Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model. J Clin Invest 1998; 102:1413.
- http://www.ncbi.nlm.nih.gov/gene (Accessed on July 10, 2013).
- Bee KJ, Wilkes DC, Devereux RB, et al. TGFβRIIb mutations trigger aortic aneurysm pathogenesis by altering transforming growth factor β2 signal transduction. Circ Cardiovasc Genet 2012; 5:621.
- LeMaire SA, McDonald ML, Guo DC, et al. Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet 2011; 43:996.
- Guo DC, Pannu H, Tran-Fadulu V, et al. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet 2007; 39:1488.
- Kuzmik GA, Sang AX, Elefteriades JA. Natural history of thoracic aortic aneurysms. J Vasc Surg 2012; 56:565.
- Griepp RB, Ergin MA, Galla JD, et al. Natural history of descending thoracic and thoracoabdominal aneurysms. Ann Thorac Surg 1999; 67:1927.
- Sueyoshi E, Sakamoto I, Hayashi K, et al. Growth rate of aortic diameter in patients with type B aortic dissection during the chronic phase. Circulation 2004; 110:II256.
- Hansen PA, Richards JM, Tambyraja AL, et al. Natural history of thoraco-abdominal aneurysm in high-risk patients. Eur J Vasc Endovasc Surg 2010; 39:266.
- Davies RR, Goldstein LJ, Coady MA, et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size. Ann Thorac Surg 2002; 73:17.
- Bonser RS, Pagano D, Lewis ME, et al. Clinical and patho-anatomical factors affecting expansion of thoracic aortic aneurysms. Heart 2000; 84:277.
- Dapunt OE, Galla JD, Sadeghi AM, et al. The natural history of thoracic aortic aneurysms. J Thorac Cardiovasc Surg 1994; 107:1323.
- Shang EK, Nathan DP, Sprinkle SR, et al. Peak wall stress predicts expansion rate in descending thoracic aortic aneurysms. Ann Thorac Surg 2013; 95:593.
- Davies RR, Kaple RK, Mandapati D, et al. Natural history of ascending aortic aneurysms in the setting of an unreplaced bicuspid aortic valve. Ann Thorac Surg 2007; 83:1338.
- La Canna G, Ficarra E, Tsagalau E, et al. Progression rate of ascending aortic dilation in patients with normally functioning bicuspid and tricuspid aortic valves. Am J Cardiol 2006; 98:249.
- Shang EK, Nathan DP, Boonn WW, et al. A modern experience with saccular aortic aneurysms. J Vasc Surg 2013; 57:84.
- Elefteriades JA. Indications for aortic replacement. J Thorac Cardiovasc Surg 2010; 140:S5.
- Pressler V, McNamara JJ. Thoracic aortic aneurysm: natural history and treatment. J Thorac Cardiovasc Surg 1980; 79:489.
- Crawford ES, DeNatale RW. Thoracoabdominal aortic aneurysm: observations regarding the natural course of the disease. J Vasc Surg 1986; 3:578.
- Juvonen T, Ergin MA, Galla JD, et al. Prospective study of the natural history of thoracic aortic aneurysms. Ann Thorac Surg 1997; 63:1533.
- Coady MA, Rizzo JA, Hammond GL, et al. Surgical intervention criteria for thoracic aortic aneurysms: a study of growth rates and complications. Ann Thorac Surg 1999; 67:1922.
- Kim JB, Kim K, Lindsay ME, et al. Risk of rupture or dissection in descending thoracic aortic aneurysm. Circulation 2015; 132:1620.
- Griepp RB, Ergin MA, Lansman SL, et al. The natural history of thoracic aortic aneurysms. Semin Thorac Cardiovasc Surg 1991; 3:258.
- Davies RR, Gallo A, Coady MA, et al. Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysms. Ann Thorac Surg 2006; 81:169.
- Coady MA, Rizzo JA, Hammond GL, et al. What is the appropriate size criterion for resection of thoracic aortic aneurysms? J Thorac Cardiovasc Surg 1997; 113:476.
- Koullias G, Modak R, Tranquilli M, et al. Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta. J Thorac Cardiovasc Surg 2005; 130:677.
- Pape LA, Tsai TT, Isselbacher EM, et al. Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2007; 116:1120.
- DEFINITION AND CLASSIFICATION
- ETIOLOGY AND RISK FACTORS
- At risk for atherosclerosis
- Presence of other aneurysms
- Prior aortic dissection
- Chest trauma
- - Infectious
- - Inflammatory disorders
- Genetic predisposition
- - Syndromic connective tissue disorders
- Marfan syndrome
- Ehlers-Danlos syndrome
- Loeys-Dietz syndrome
- - Turner syndrome
- - Nonsyndromic disorders
- Familial TAAD
- Bicuspid aortic valve
- Aneurysm-osteoarthritis syndrome
- NATURAL HISTORY
- SUMMARY AND RECOMMENDATIONS