Medical Treatment of Thoracic Aortic Pathologies

  • Alan C. BravermanEmail author


Thoracic aortic aneurysm disease is an important cause of morbidity and mortality. Recognizing the specific disorder responsible for the condition informs management, including screening of first-degree relatives, imaging strategies, and determining the timing of prophylactic surgery or endovascular repair. Pharmacologic therapy typically involves beta adrenergic blocking agents, which slow the heart rate and lower blood pressure. Hemodynamic benefits of beta blockers may lessen stress on the aortic wall and are beneficial in Marfan syndrome and aortic dissection. Angiotensin receptor blockers have demonstrated benefit in patients with Marfan syndrome, and ongoing trials worldwide using these agents hold the promise of additional therapy to potentially retard aortic growth. Research into underlying mechanisms of disease utilizing animal models may translate into therapies which target various signaling pathways involved in these disorders. Lifestyle modification impacting intensity of physical activity, employment, and pregnancy are important aspects of medical management of thoracic aortic diseases. Long-term imaging surveillance, before surgery and after repair, is necessary to detect aortic developing pathology.


Lifestyle Pharmacology Aortopathy Mutation 


  1. 1.
    Braverman A. Diseases of the aorta. In: Mann D, Bonow R, Zipes D, Libby P, editors. Braunwald’s heart disease. 10th ed. Philadelphia: Elsevier Inc.; 2014. in press.Google Scholar
  2. 2.
    Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47:476–85.CrossRefGoogle Scholar
  3. 3.
    Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Cooper TK, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science. 2006;312(5770):117–21.CrossRefGoogle Scholar
  4. 4.
    Hiratzka LF, Bakris GL, Beckman JA, Bersin RN, Carr VF, Casey DE Jr, 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. J Am Coll Cardiol. 2010;55:127–9.CrossRefGoogle Scholar
  5. 5.
    Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, et al. Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006;355:788–98.CrossRefGoogle Scholar
  6. 6.
    Braverman A. The bicuspid aortic valve and associated aortic disease. In: Otto C, Bonow R, editors. Valvular heart disease: a companion to Braunwald’s heart disease. 3rd ed. Philadelphia: Saunders-Elsevier; 2013. p. 179–98.Google Scholar
  7. 7.
    Lindsay ME, Schepers D, Bolar NA, Doyle J, Gallo E, Kempers MJE, Fishman EK, Chen Y, Myers L, Bjeda D, Oswald G, Anderlid BM, Yang M, Bongers E, Timmermans J, Mortier G, Braverman AC, Canham N, Brunner H, Byers P, Van Laer L, Dietz HC, Loeys BL. Loss of function mutations in TGFB2 cause Loeys-Dietz syndrome. Nat Genet. 2012;44:922–7.CrossRefGoogle Scholar
  8. 8.
    Elefteriades J. Does medical therapy for thoracic aortic aneurysms really work? Are beta-blockers truly indicated? Pro. Cardiol Clin. 2010;28:255–60.CrossRefGoogle Scholar
  9. 9.
    Liao S, Elmariah S, S van der Z, Sealove B, Fuster V. Does medical therapy for thoracic aortic aneurysms really work? Are beta-blockers truly indicated? CON. Cardiol Clin. 2010;28:261–9.CrossRefGoogle Scholar
  10. 10.
    Shores J, Berger K, Murphy E, Pyeritz R. Progression of aortic dilatation and the benefit of long-term β-adrenergic blockade in Marfan’s syndrome. N Engl J Med. 1994;330:1335–41.CrossRefGoogle Scholar
  11. 11.
    Genoni M, Paul M, Jenni R, Gravers K, Seifert B, Turina M. Chronic β-blocker therapy improves outcome and reduces treatment in chronic type B aortic dissection. Eur J Cardiothorac Surg. 2001;19:606–10.CrossRefGoogle Scholar
  12. 12.
    Suzuki T, Isselbacher E, Nienaber CA, Pyeritz R, Eagle KA, Tsai TT, Cooper JV, Januzzi JL Jr, Braverman AC, Montgomery DG, Fattori R, Pape L, Harris KM, Booher AN, Oh JK, Peterson M, Ramanath VS, Forehlich JB. Type-selective benefits of medications in treatment of acute aortic dissection. From the International Registry of Acute Aortic Dissection (IRAD). Am J Cardiol. 2012;109:122–7.CrossRefGoogle Scholar
  13. 13.
    Groenink M, Roos AD, Mulder BJM, Spaan JAE, Wall EEVD. Changes in aortic distensibility and beta-blocker therapy in the Marfan syndrome. Pulse. 1998;9149:203–8.Google Scholar
  14. 14.
    Silverman DI, Burong KJ, Gray J, et al. Life expectancy in the Marfan syndrome. Am J Cardiol. 1995;75:157–60.CrossRefGoogle Scholar
  15. 15.
    Chu LC, Johnson PT, Dietz HC, Fishman EK. CT angiographic evaluation of genetic vascular disease: role in detection, staging, and management of complex vascular pathologic conditions. Am J Radiol. 2014;202:1120–9.Google Scholar
  16. 16.
    Habashi JP, Doyle JJ, Holm TM, Aziz H, Schoenhoff F, Bedja D, et al. Angiotensin II type 2 receptor signaling attenuates aortic aneurysm in mice through ERK. Science. 2011;332:361–5.CrossRefGoogle Scholar
  17. 17.
    Brooke BS, Habashi JP, Judge DP, Patel N, Loeys B, Dietz HC. Angiotensin II blockade and aortic-root dilation in Marfan’s syndrome. N Engl J Med. 2008;358:2787–95.CrossRefGoogle Scholar
  18. 18.
    Lindsay M, Dietz H. Lessons on the pathogenesis of aneurysm from heritable conditions. Nature. 2011;473:308–16.CrossRefGoogle Scholar
  19. 19.
    Lacro RV, Dietz HC, Wruck LM, Bradley TJ, Colan SD, Devereux RB, Klein GL, Li JS, Minich LL, Paridon SM, Pearson GD, Printz BF, Pyeritz RE, Radojewski E, Roman MJ, Saul JP, Stylianou MP, Mahony L, Pediatric Heart Network Investigators. Rationale and design of a randomized clinical trial of beta-blocker therapy (atenolol) versus angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome. Am Heart J. 2007;154:624–31.CrossRefGoogle Scholar
  20. 20.
    Chiu HH, Wu MH, Wang JK, Lu CW, Chiu SN, Chen CA, Lin MT, Hu FC. Losartan added to β-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study. Mayo Clin Proc. 2013;88:271–6.CrossRefGoogle Scholar
  21. 21.
    Groenink M, den Hartog AW, Franken R, Radonic T, de Waard V, Timmermans J, et al. Losartan reduces aortic dilatation rate in adults with Marfan syndrome: a randomized controlled trial. Eur Heart J. 2013;34:3491–50.CrossRefGoogle Scholar
  22. 22.
    Lacro RV, Dietz HC, Sleeper LA, Yetman AT, Bradley TJ, Colan SD, et al. For the pediatric heart network investigators. Randomized trial of atenolol versus losartan in children and young adults with Marfan syndrome. N Engl J Med. 2014;371:2061–71.CrossRefGoogle Scholar
  23. 23.
    Milleron O, Arnoult F, Ropers J, Aegerter P, Detaint D, Delorme G, et al. Marfan Sartan: a randomized, double-blind, placebo-controlled trial. Eur Heart J. 2015;36:2160–6.CrossRefGoogle Scholar
  24. 24.
    Forteza A, Evangelista A, Sanchez V, Teixido-Tura G, Sanz P, Gutierrez L, et al. Efficacy of losartan vs. atenolol for the prevention of aortic dilation in Marfan syndrome: a randomized clinical trial. Eur Heart J. 2016;37:978–85.CrossRefGoogle Scholar
  25. 25.
    Pitcher A, Emberson J, Lacro RV, Sleeper LA, Sytlianou M, Mahony L, et al. Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: a report from the Marfan Treatment Trialists Collaboration. Am Heart J. 2015;169:605–12.CrossRefGoogle Scholar
  26. 26.
    Hartog AW, Franken R, Zwinderman AK, Groenink M, Mulder BJM. Current and future pharmacologic treatment strategies with regard to aortic disease in Marfan syndrome. Expert Opin Pharmacother. 2012;13:647–62.CrossRefGoogle Scholar
  27. 27.
    Yetman AT, Bornemeier RA, McCrindle BW. Usefulness of enalapril versus propranolol or atenolol for prevention of aortic dilation in patients with Marfan syndrome. Am J Cardiol. 2005;95:1125–7.CrossRefGoogle Scholar
  28. 28.
    Gomez D, Al Haj Zen A, Borges LF, Philippe M, Gutierrez PS, Jondeau G, et al. Syndromic and non-syndromic aneurysms of the human ascending aorta share activation of the Smad2 pathway. J Pathol. 2009;218:131–42.CrossRefGoogle Scholar
  29. 29.
    Gallo EM, Loch DC, Habashi JP, et al. Angiotensin II-dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis. J Clin Invest. 2014;124:448–60.CrossRefGoogle Scholar
  30. 30.
    Moltzer E, Essers J, Van Esch JHM, Roos-Hesselink JW, Danser AHJ. The role of the renin-angiotensin system in thoracic aortic aneurysms: clinical implications. Pharm Ther. 2011;131:50–60.CrossRefGoogle Scholar
  31. 31.
    Chung AWY, Yang HHC, Radomski MW, Van Breemen C. Long-term doxycycline is more effective than atenolol to prevent thoracic aortic aneurysm in Marfan syndrome through the inhibition of matrix metalloproteinase-2 and -9. Circ Res. 2008;102:73–85.CrossRefGoogle Scholar
  32. 32.
    McLoughlin D, McGuinness J, Byrne J, Terzo E, Huuskonen V, McAllister H, et al. Pravastatin reduces Marfan aortic dilation. Circulation. 2011;124:S168–73.CrossRefGoogle Scholar
  33. 33.
    Stein IS, Berger J, Tranquilli M, et al. Statin therapy and the natural history of thoracic aortic aneurysm. Am J Cardiol. 2013;112:1240–5.CrossRefGoogle Scholar
  34. 34.
    Maron B, Ackerman M, Nishimura R, Pyeritz RE, Towbin JA, Udelson JE. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol. 2005;45:1340–5.CrossRefGoogle Scholar
  35. 35.
    Braverman AC, Harris KM, Kovacs R, Baron BJ, Scientific Statement AHA/ACC. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 7: aortic diseases, including Marfan syndrome. J Am Coll Cardiol. 2015;66:2398–405.CrossRefGoogle Scholar
  36. 36.
    Pelliccia A, Fagard R, Bjørnstad HH, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease. A consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J. 2005;26:1422–45.CrossRefGoogle Scholar
  37. 37.
    Chaddha A, Kline-Rogers E, Woznicki E, Brook R, Housholder-Hughes S, Braverman AC, Pitler L, Hirsch A, Eagle KA. Activity recommendations for post-aortic dissection patients. Circulation. 2014;130:140–2.CrossRefGoogle Scholar
  38. 38.
    Mayerick C, Carré F, Elefteriades J. Aortic dissection and sport: physiologic and clinical understanding provide an opportunity to save young lives. J Cardiovasc Surg. 2010;51:669–81.Google Scholar
  39. 39.
    Babae Biqi M, Aslani A. Aortic root size and prevalence of aortic regurgitation in elite strength trained athletes. Am J Cardiol. 2007;100:528–30.CrossRefGoogle Scholar
  40. 40.
    Hatzaras I, Tranquilli M, Coady M, Barrett PM, Bible J, Elefteriades JA. Weight lifting and aortic dissection: more evidence for a connection. Cardiology. 2007;107:103–6.CrossRefGoogle Scholar
  41. 41.
    Velvin G, Bathen T, Rand-Hendriksen S, Geirdal AO. Work participation in adults with Marfan syndrome: demographic characteristics, MFS related health symptoms, chronic pain, and fatigue. Am J Med Genet Part A. 2015;167:3082–90.CrossRefGoogle Scholar
  42. 42.
    Chaddha A, Eagle KA, Braverman AC, Kline-Rogers E, Hirsch AT, Brook R, et al. Exercise and physical activity for the post-aortic dissection patient: the clinician’s conundrum. Clin Cardiol. 2015;38:647–51.CrossRefGoogle Scholar
  43. 43.
    Chaddha A, Kline-Rogers E, Braverman AC, Erickson SR, Jackson EA, Franklin BA, et al. Survivors of aortic dissection: activity, mental health, and sexual function. Clin Cardiol. 2015;38:652–9.CrossRefGoogle Scholar
  44. 44.
    Nasiell J, Norman M, Lindqvist PG, Malmstedt J, Bottinga R, Blennow M. Aortic dissection in pregnancy: a life-threatening disease and a diagnosis of worth considering. Eur J Obstet Gynecol Reprod Biol. 2010;149:120–1.CrossRefGoogle Scholar
  45. 45.
    Goland S, Elkayam U. Cardiovascular problems in pregnant women with Marfan syndrome. Circulation. 2009;119:619–23.CrossRefGoogle Scholar
  46. 46.
    Donnelly RT, Pinto NM, Kocolas I, Yetman AT. The immediate and long-term impact of pregnancy on aortic growth rate and mortality in women with Marfan syndrome. J Am Coll Cardiol. 2012;60:224–9.CrossRefGoogle Scholar
  47. 47.
    Williams D, Lindley KJ, Russo M, Habashi J, Dietz HC, Braverman AC. Pregnancy after aortic root replacement in Marfan syndrome: a survey and literature review. J Am Coll Cardiol. 2016;67:904.CrossRefGoogle Scholar
  48. 48.
    Braverman A, Harris K, Pyeritz R, Hutchison S, Pitler L, Evangelista A, et al. Aortic dissection during pregnancy: results from the International Registry of Acute Aortic Dissection (IRAD). J Am Coll Cardiol. 2012;59:A467.CrossRefGoogle Scholar
  49. 49.
    Regalado ES, Guo DC, Estrera AL, Buja LM, Milewicz DM. Acute aortic dissections with pregnancy in women with ACTA2 mutations. Am J Med Genet A. 2014;164:106–12.CrossRefGoogle Scholar
  50. 50.
    Braverman AC, Moon MR, Geraghty P, Willing MC, Bach C, Kouchoukos NT. Pregnancy after aortic root replacement in Loeys-Dietz syndrome: high risk of aortic dissection. Am J Med Genet A. 2016;170:2177–80.CrossRefGoogle Scholar
  51. 51.
    Lindsay ME, Dietz C. The genetic basis of aortic aneurysm. Cold Spring Harb Perspect Med. 2014;4:a015909.CrossRefGoogle Scholar
  52. 52.
    Arslan-Kirchner M, Arbustini E, Boileau C, Charron P, Child AH, Collod-Beroud G, et al. Clinical utility gene card for: hereditary thoracic aortic aneurysm and dissection including next-generation sequencing-based approaches. Eur J Hum Genet. 2016;24:1–5.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Cardiovascular Division, Department of MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Marfan Syndrome and Aortopathy CenterSt. LouisUSA
  3. 3.Inpatient Cardiology FirmSt. LouisUSA

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