J Cardiovasc Ultrasound.  2015 Jun;23(2):59-69. 10.4250/jcu.2015.23.2.59.

Aortic Stenosis: Changing Disease Concepts

• Rashedi N
• Otto CM

• KMID: 1806912
• DOI: http://doi.org/10.4250/jcu.2015.23.2.59

Abstract

Aortic stenosis (AS) occurs in almost 10% of adults over age 80 years with a mortality about 50% at 2 years unless outflow obstruction is relieved by aortic valve replacement (AVR). Development of AS is associated with anatomic, clinical and genetic risk factors including a bicuspid valve in 50%; clinical factors that include older age, hypertension, smoking, diabetes and elevated serum lipoprotein(a) [Lp(a)] levels; and genetic factors such as a polymorphism in the Lp(a) locus. Early stages of AS are characterized by focal areas of leaflet thickening and calcification. The rate of hemodynamic progression is variable but eventual severe AS is inevitable once even mild valve obstruction is present. There is no specific medical therapy to prevent leaflet calcification. Basic principles of medical therapy for asymptomatic AS are patient education, periodic echocardiographic and clinical monitoring, standard cardiac risk factor evaluation and modification and treatment of hypertension or other comorbid conditions. When severe AS is present, a careful evaluation for symptoms is needed, often with an exercise test to document symptom status and cardiac reserve. In symptomatic patients with severe AS, AVR improves survival and relieves symptoms. In asymptomatic patients with severe AS, AVR also is appropriate if ejection fraction is < 50%, disease progression is rapid or AS is very severe (aortic velocity > 5 m/s). The choice of surgical or transcatheter AVR depends on the estimated surgical risk plus other factors such as frailty, other organ system disease and procedural specific impediments.

Keyword

Aortic stenosis; Valve replacement; Echocardiography

MeSH Terms

Adult
Aortic Valve
Aortic Valve Stenosis*
Disease Progression
Echocardiography
Exercise Test
Hemodynamics
Humans
Hypertension
Lipoprotein(a)
Mitral Valve
Mortality
Patient Education as Topic
Risk Factors
Smoke
Smoking
Lipoprotein(a)
Smoke

Figure

• 

  Fig. 1 Evaluation and management of the patient with low-flow low-gradient aortic stenosis. The AHA/ACC class recommendation (I, IIa, or IIb) is shown in parentheses corresponding to Table 3. AHA/ACC: 2014 American Heart Association and American College of Cardiology Guidelines, AS: aortic stenosis, AVA: aortic valve area, AVR: aortic valve replacement which may be either surgical or transcatheter, DSE: dobutamine stress echocardiography (low dose), EF: ejection fraction, SVI: stroke volume indexed to body size, Vmax: maximum aortic velocity.

• 

  Fig. 2 Timing of aortic valve replacement in adults with asymptomatic aortic stenosis. The AHA/ACC class recommendation (I, IIa, or IIb) is shown in parentheses corresponding to Table 3. AHA/ACC: 2014 American Heart Association and American College of Cardiology Guidelines, AS: aortic stenosis, AVR: aortic valve replacement which may be either surgical or transcatheter, BP: blood pressure, EF: ejection fraction, ETT: exercise treadmill test, ex: exercise, Vmax: maximum aortic velocity.

Reference

1. Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999; 341:142–147.

2. Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, Fontana GP, Dewey TM, Thourani VH, Pichard AD, Fischbein M, Szeto WY, Lim S, Greason KL, Teirstein PS, Malaisrie SC, Douglas PS, Hahn RT, Whisenant B, Zajarias A, Wang D, Akin JJ, Anderson WN, Leon MB. PARTNER Trial Investigators. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012; 366:1686–1695.

3. Eveborn GW, Schirmer H, Heggelund G, Lunde P, Rasmussen K. The evolving epidemiology of valvular aortic stenosis. the Tromsø study. Heart. 2013; 99:396–400.

4. Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol. 1997; 29:630–634.

5. Otto CM, Prendergast B. Aortic-valve stenosis--from patients at risk to severe valve obstruction. N Engl J Med. 2014; 371:744–756.

6. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD. ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129:2440–2492.

7. Otto CM, Burwash IG, Legget ME, Munt BI, Fujioka M, Healy NL, Kraft CD, Miyake-Hull CY, Schwaegler RG. Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation. 1997; 95:2262–2270.

8. Rosenhek R, Binder T, Porenta G, Lang I, Christ G, Schemper M, Maurer G, Baumgartner H. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000; 343:611–617.

9. Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation. 2005; 111:920–925.

10. Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol. 2010; 55:2789–2800.

11. Michelena HI, Desjardins VA, Avierinos JF, Russo A, Nkomo VT, Sundt TM, Pellikka PA, Tajik AJ, Enriquez-Sarano M. Natural history of asymptomatic patients with normally functioning or minimally dysfunctional bicuspid aortic valve in the community. Circulation. 2008; 117:2776–2784.

12. Tzemos N, Therrien J, Yip J, Thanassoulis G, Tremblay S, Jamorski MT, Webb GD, Siu SC. Outcomes in adults with bicuspid aortic valves. JAMA. 2008; 300:1317–1325.

13. Owens DS, O'Brien KD. Clinical and genetic risk factors for calcific valve disease. In : Otto CM, Bonow RO, editors. Valvular heart disease: a companion to Braunwald's heart disease. 4th ed. Philadelphia: Elsevier Science;2014. p. 53–62.

14. Probst V, Le Scouarnec S, Legendre A, Jousseaume V, Jaafar P, Nguyen JM, Chaventré A, Le Marec H, Schott JJ. Familial aggregation of calcific aortic valve stenosis in the western part of France. Circulation. 2006; 113:856–860.

15. Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, Kerr KF, Pechlivanis S, Budoff MJ, Harris TB, Malhotra R, O'Brien KD, Kamstrup PR, Nordestgaard BG, Tybjaerg-Hansen A, Allison MA, Aspelund T, Criqui MH, Heckbert SR, Hwang SJ, Liu Y, Sjogren M, van der Pals J, Kälsch H, Mühleisen TW, Nöthen MM, Cupples LA, Caslake M, Di Angelantonio E, Danesh J, Rotter JI, Sigurdsson S, Wong Q, Erbel R, Kathiresan S, Melander O, Gudnason V, O'Donnell CJ, Post WS. CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013; 368:503–512.

16. Arsenault BJ, Boekholdt SM, Dubé MP, Rhéaume E, Wareham NJ, Khaw KT, Sandhu MS, Tardif JC. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet. 2014; 7:304–310.

17. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein (a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014; 63:470–477.

18. Katz R, Wong ND, Kronmal R, Takasu J, Shavelle DM, Probstfield JL, Bertoni AG, Budoff MJ, O'Brien KD. Features of the metabolic syndrome and diabetes mellitus as predictors of aortic valve calcification in the Multi-Ethnic Study of Atherosclerosis. Circulation. 2006; 113:2113–2119.

19. Owens DS, Katz R, Takasu J, Kronmal R, Budoff MJ, O'Brien KD. Incidence and progression of aortic valve calcium in the Multi-ethnic Study of Atherosclerosis (MESA). Am J Cardiol. 2010; 105:701–708.

20. Smith JG, Luk K, Schulz CA, Engert JC, Do R, Hindy G, Rukh G, Dufresne L, Almgren P, Owens DS, Harris TB, Peloso GM, Kerr KF, Wong Q, Smith AV, Budoff MJ, Rotter JI, Cupples LA, Rich S, Kathiresan S, Orho-Melander M, Gudnason V, O'Donnell CJ, Post WS, Thanassoulis G. Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Extracoronary Calcium Working Group. Association of low-density lipoprotein cholesterol-related genetic variants with aortic valve calcium and incident aortic stenosis. JAMA. 2014; 312:1764–1771.

21. Kurtz CE, Otto CM. Aortic stenosis: clinical aspects of diagnosis and management, with 10 illustrative case reports from a 25-year experience. Medicine (Baltimore). 2010; 89:349–379.

22. Novaro GM, Katz R, Aviles RJ, Gottdiener JS, Cushman M, Psaty BM, Otto CM, Griffin BP. Clinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study. J Am Coll Cardiol. 2007; 50:1992–1998.

23. Capoulade R, Magne J, Dulgheru R, Hachicha Z, Dumesnil JG, O'Connor K, Arsenault M, Bergeron S, Pierard LA, Lancellotti P, Pibarot P. Prognostic value of plasma B-type natriuretic peptide levels after exercise in patients with severe asymptomatic aortic stenosis. Heart. 2014; 100:1606–1612.

24. Lindman BR. BNP during exercise: a novel use for a familiar biomarker in aortic stenosis. Heart. 2014; 100:1567–1568.

25. Teo KK, Corsi DJ, Tam JW, Dumesnil JG, Chan KL. Lipid lowering on progression of mild to moderate aortic stenosis: meta-analysis of the randomized placebo-controlled clinical trials on 2344 patients. Can J Cardiol. 2011; 27:800–808.

26. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R. SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008; 359:1343–1356.

27. Rieck ÅE, Cramariuc D, Boman K, Gohlke-Bärwolf C, Staal EM, Lønnebakken MT, Rossebø AB, Gerdts E. Hypertension in aortic stenosis: implications for left ventricular structure and cardiovascular events. Hypertension. 2012; 60:90–97.

28. Khot UN, Novaro GM, Popović ZB, Mills RM, Thomas JD, Tuzcu EM, Hammer D, Nissen SE, Francis GS. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med. 2003; 348:1756–1763.

29. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC). European Association for Cardio-Thoracic Surgery (EACTS). Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schäfers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012; 33:2451–2496.

30. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S. PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010; 363:1597–1607.

31. Kapadia SR, Leon MB, Makkar RR, Tuzcu EM, Svensson LG, Kodali S, Webb JG, Mack MJ, Douglas PS, Thourani VH, Babaliaros VC, Herrmann HC, Szeto WY, Pichard AD, Williams MR, Fontana GP, Miller DC, Anderson WN, Smith CR, Akin JJ, Davidson MJ. PARTNER trial investigators. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015; 03. 15. [Epub]. DOI: 10.1016/S0140-6736(15)60290-2.

32. Gotzmann M, Lindstaedt M, Bojara W, Ewers A, Mügge A. Clinical outcome of transcatheter aortic valve implantation in patients with lowflow, low gradient aortic stenosis. Catheter Cardiovasc Interv. 2012; 79:693–701.

33. Tribouilloy C, Lévy F, Rusinaru D, Guéret P, Petit-Eisenmann H, Baleynaud S, Jobic Y, Adams C, Lelong B, Pasquet A, Chauvel C, Metz D, Quéré JP, Monin JL. Outcome after aortic valve replacement for low-flow/low-gradient aortic stenosis without contractile reserve on dobutamine stress echocardiography. J Am Coll Cardiol. 2009; 53:1865–1873.

34. Jander N, Minners J, Holme I, Gerdts E, Boman K, Brudi P, Chambers JB, Egstrup K, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Rossebø A, Pedersen TR, Skjærpe T, Willenheimer R, Wachtell K, Neumann FJ, Gohlke-Bärwolf C. Outcome of patients with low-gradient "severe" aortic stenosis and preserved ejection fraction. Circulation. 2011; 123:887–895.

35. Pibarot P, Dumesnil JG. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation. 2009; 119:1034–1048.

36. Ozkan A, Hachamovitch R, Kapadia SR, Tuzcu EM, Marwick TH. Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction. Circulation. 2013; 128:622–631.

37. Eleid MF, Sorajja P, Michelena HI, Malouf JF, Scott CG, Pellikka PA. Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival. Circulation. 2013; 128:1781–1789.

38. Rosenhek R, Zilberszac R, Schemper M, Czerny M, Mundigler G, Graf S, Bergler-Klein J, Grimm M, Gabriel H, Maurer G. Natural history of very severe aortic stenosis. Circulation. 2010; 121:151–156.

39. Kang DH, Kim JH, Rim JH, Kim MJ, Yun SC, Song JM, Song H, Choi KJ, Song JK, Lee JW. Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation. Circulation. 2009; 119:797–804.

40. Connolly HM, Oh JK, Schaff HV, Roger VL, Osborn SL, Hodge DO, Tajik AJ. Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction: result of aortic valve replacement in 52 patients. Circulation. 2000; 101:1940–1946.

41. Clavel MA, Webb JG, Rodés-Cabau J, Masson JB, Dumont E, De Larochellière R, Doyle D, Bergeron S, Baumgartner H, Burwash IG, Dumesnil JG, Mundigler G, Moss R, Kempny A, Bagur R, Bergler-Klein J, Gurvitch R, Mathieu P, Pibarot P. Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction. Circulation. 2010; 122:1928–1936.

42. Rosenhek R, Baumgartner H. Aortic stenosis. In : Otto CM, Bonow RO, editors. Valvular heart disease: a companion to Braunwald's heart disease. 4th ed. Philadelphia: Elsevier Science;2014. p. 139–162.

43. Walther T, Blumenstein J, van Linden A, Kempfert J. Contemporary management of aortic stenosis: surgical aortic valve replacement remains the gold standard. Heart. 2012; 98:Suppl 4. iv23–iv29.

44. Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, Thourani VH, Babaliaros VC, Webb JG, Herrmann HC, Bavaria JE, Kodali S, Brown DL, Bowers B, Dewey TM, Svensson LG, Tuzcu M, Moses JW, Williams MR, Siegel RJ, Akin JJ, Anderson WN, Pocock S, Smith CR, Leon MB. Trial Investigators. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012; 366:1696–1704.

45. Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ. PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011; 364:2187–2198.

46. Mack MJ, Leon MB, Smith CR, Miller DC, Moses JW, Tuzcu EM, Webb JG, Douglas PS, Anderson WN, Blackstone EH, Kodali SK, Makkar RR, Fontana GP, Kapadia S, Bavaria J, Hahn RT, Thourani VH, Babaliaros V, Pichard A, Herrmann HC, Brown DL, Williams M, Davidson MJ, Svensson LG, Akin J. PARTNER 1 trial investigators. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial. Lancet. 2015; 03. 15. [Epub]. DOI: 10.1016/S0140-6736(15)60308-7.

47. Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J Jr, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S, Oh JK. U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014; 370:1790–1798.

48. Thyregod HG, Steinbrüchel DA, Ihlemann N, Nissen H, Kjeldsen BJ, Petursson P, Chang Y, Franzen OW, Engstrøm T, Clemmensen P, Hansen PB, Andersen LW, Olsen PS, Søndergaard L. Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Valve Stenosis: One-year Results from the All-comers Nordic Aortic Valve Intervention (NOTION) Randomized Clinical Trial. J Am Coll Cardiol. 2015; 03. 05. [Epub]. DOI: 10.1016/j.jacc.2015.03.014.

49. Khawaja MZ, Williams R, Hung J, Arri S, Asrress KN, Bolter K, Wilson K, Young CP, Bapat V, Hancock J, Thomas M, Redwood S. Impact of preprocedural mitral regurgitation upon mortality after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. Heart. 2014; 100:1799–1803.