Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Clinical manifestations and diagnosis of low gradient severe aortic stenosis

Dania Mohty, MD, PhD
Section Editor
Patricia A Pellikka, MD, FACC, FAHA, FASE
Deputy Editor
Susan B Yeon, MD, JD, FACC


Degenerative valvular heart disease (VHD) is common and is the third most frequent cause of cardiac disease after hypertension and coronary artery disease in developed countries with aging populations. Among patients with at least moderate VHD in developed countries, aortic valve stenosis (AS) is most common, followed by mitral regurgitation then aortic regurgitation and finally mitral stenosis [1].

For appropriate diagnosis and management of AS, it is crucial to assess the severity of AS as accurately as possible. However, the diagnosis and evaluation of AS is challenging due to a variety of pitfalls. These include discrepancies between severity of AS and patient symptoms, between transvalvular mean pressure gradient and aortic valve area, and between echocardiography and other imaging modalities. In addition, a number of confounding factors and technical issues affect the assessment of AS, including the presence of concurrent conditions such as uncontrolled hypertension, rapid atrial fibrillation, left ventricular dysfunction, and significant mitral regurgitation or stenosis, as well as the occurrence of measurement errors.

Issues relating to the clinical manifestations and diagnosis of low gradient AS will be reviewed here. Management and prognosis of low gradient severe AS, and the clinical presentation and management of classical high gradient severe AS are discussed separately. (See "Clinical manifestations and diagnosis of aortic stenosis in adults" and "Medical management of asymptomatic aortic stenosis in adults" and "Indications for valve replacement in aortic stenosis in adults", section on 'Low gradient aortic stenosis' and "Management and prognosis of low gradient aortic stenosis".)


High gradient severe AS — The 2014 American Heart Association/American College of Cardiology valvular heart disease guidelines identify severe aortic stenosis (AS) by the presence of an aortic transvalvular velocity ≥4 m/s and/or mean transvalvular pressure gradient ≥40 mmHg; the aortic valve area (AVA) is typically ≤1 cm2 (with AVA indexed to body surface area ≤0.6 cm2/m2), although it may be larger with concurrent AS and aortic regurgitation (table 1) [2]; similar criteria are included in the 2012 European Society of Cardiology valve disease guidelines [3]. However, these high velocity and high pressure gradient criteria are valid only in the presence of a normal stroke volume. At least 50 percent of patients with symptomatic severe AS have high-gradient AS.

Types of low flow and/or low gradient AS — Low flow (stroke volume indexed to body surface area ≤35mL/m2) severe AS and low gradient (transvalvular mean pressure gradient ≤40 mmHg) severe AS are partially overlapping categories of AS:

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: May 18, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J 2003; 24:1231.
  2. Nishimura RA, Otto CM, Bonow RO, et al. 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. J Am Coll Cardiol 2014; 63:2438.
  3. 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, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012; 33:2451.
  4. Pibarot P, Dumesnil JG. Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction. J Am Coll Cardiol 2012; 60:1845.
  5. Clavel MA, Magne J, Pibarot P. Low-gradient aortic stenosis. Eur Heart J 2016; 37:2645.
  6. Adda J, Mielot C, Giorgi R, et al. Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunction as assessed by speckle-tracking echocardiography: a multicenter study. Circ Cardiovasc Imaging 2012; 5:27.
  7. Lancellotti P, Magne J, Donal E, et al. Clinical outcome in asymptomatic severe aortic stenosis: insights from the new proposed aortic stenosis grading classification. J Am Coll Cardiol 2012; 59:235.
  8. Minners J, Allgeier M, Gohlke-Baerwolf C, et al. Inconsistent grading of aortic valve stenosis by current guidelines: haemodynamic studies in patients with apparently normal left ventricular function. Heart 2010; 96:1463.
  9. Mohty D, Magne J, Deltreuil M, et al. Outcome and impact of surgery in paradoxical low-flow, low-gradient severe aortic stenosis and preserved left ventricular ejection fraction: a cardiac catheterization study. Circulation 2013; 128:S235.
  10. Eleid MF, Sorajja P, Michelena HI, et al. Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival. Circulation 2013; 128:1781.
  11. Herrmann HC, Pibarot P, Hueter I, et al. Predictors of mortality and outcomes of therapy in low-flow severe aortic stenosis: a Placement of Aortic Transcatheter Valves (PARTNER) trial analysis. Circulation 2013; 127:2316.
  12. Lancellotti P, Donal E, Magne J, et al. Impact of global left ventricular afterload on left ventricular function in asymptomatic severe aortic stenosis: a two-dimensional speckle-tracking study. Eur J Echocardiogr 2010; 11:537.
  13. Dahl JS, Eleid MF, Pislaru SV, et al. Development of paradoxical low-flow, low-gradient severe aortic stenosis. Heart 2015; 101:1015.
  14. Eleid MF, Nishimura RA, Borlaug BA, Sorajja P. Invasive measures of afterload in low gradient severe aortic stenosis with preserved ejection fraction. Circ Heart Fail 2013; 6:703.
  15. Antonini-Canterin F, Huang G, Cervesato E, et al. Symptomatic aortic stenosis: does systemic hypertension play an additional role? Hypertension 2003; 41:1268.
  16. Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation 2007; 115:2856.
  17. Briand M, Dumesnil JG, Kadem L, et al. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment. J Am Coll Cardiol 2005; 46:291.
  18. Magne J, Mohty D, Boulogne C, et al. Prognostic impact of global left ventricular hemodynamic afterload in severe aortic stenosis with preserved ejection fraction. Int J Cardiol 2015; 180:158.
  19. Minners J, Allgeier M, Gohlke-Baerwolf C, et al. Inconsistencies of echocardiographic criteria for the grading of aortic valve stenosis. Eur Heart J 2008; 29:1043.
  20. Moretti M, Fabris E, Morosin M, et al. Prognostic significance of atrial fibrillation and severity of symptoms of heart failure in patients with low gradient aortic stenosis and preserved left ventricular ejection fraction. Am J Cardiol 2014; 114:1722.
  21. Rezzoug N, Vaes B, Pasquet A, et al. Prevalence and Prognostic Impact of Valve Area-Gradient Patterns in Patients ≥80 Years With Moderate-to-Severe Aortic Stenosis (from the Prospective BELFRAIL Study). Am J Cardiol 2015; 116:925.
  22. Clavel MA, Ennezat PV, Maréchaux S, et al. Stress echocardiography to assess stenosis severity and predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis and preserved LVEF. JACC Cardiovasc Imaging 2013; 6:175.
  23. Blais C, Burwash IG, Mundigler G, et al. Projected valve area at normal flow rate improves the assessment of stenosis severity in patients with low-flow, low-gradient aortic stenosis: the multicenter TOPAS (Truly or Pseudo-Severe Aortic Stenosis) study. Circulation 2006; 113:711.
  24. Messika-Zeitoun D, Aubry MC, Detaint D, et al. Evaluation and clinical implications of aortic valve calcification measured by electron-beam computed tomography. Circulation 2004; 110:356.
  25. Cueff C, Serfaty JM, Cimadevilla C, et al. Measurement of aortic valve calcification using multislice computed tomography: correlation with haemodynamic severity of aortic stenosis and clinical implication for patients with low ejection fraction. Heart 2011; 97:721.
  26. Clavel MA, Messika-Zeitoun D, Pibarot P, et al. The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study. J Am Coll Cardiol 2013; 62:2329.
  27. Clavel MA, Pibarot P, Messika-Zeitoun D, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol 2014; 64:1202.
  28. Clavel MA, Malouf J, Messika-Zeitoun D, et al. Aortic valve area calculation in aortic stenosis by CT and Doppler echocardiography. JACC Cardiovasc Imaging 2015; 8:248.
  29. Kamperidis V, van Rosendael PJ, Katsanos S, et al. Low gradient severe aortic stenosis with preserved ejection fraction: reclassification of severity by fusion of Doppler and computed tomographic data. Eur Heart J 2015; 36:2087.
  30. Tandon A, Grayburn PA. Imaging of low-gradient severe aortic stenosis. JACC Cardiovasc Imaging 2013; 6:184.
  31. Chambers J, Bach D, Dumesnil J, et al. Crossing the aortic valve in severe aortic stenosis: no longer acceptable? J Heart Valve Dis 2004; 13:344.
  32. Omran H, Schmidt H, Hackenbroch M, et al. Silent and apparent cerebral embolism after retrograde catheterisation of the aortic valve in valvular stenosis: a prospective, randomised study. Lancet 2003; 361:1241.
  33. Bergler-Klein J, Mundigler G, Pibarot P, et al. B-type natriuretic peptide in low-flow, low-gradient aortic stenosis: relationship to hemodynamics and clinical outcome: results from the Multicenter Truly or Pseudo-Severe Aortic Stenosis (TOPAS) study. Circulation 2007; 115:2848.
  34. Lee SP, Kim YJ, Kim JH, et al. Deterioration of myocardial function in paradoxical low-flow severe aortic stenosis: two-dimensional strain analysis. J Am Soc Echocardiogr 2011; 24:976.
  35. Herrmann S, Störk S, Niemann M, et al. Low-gradient aortic valve stenosis myocardial fibrosis and its influence on function and outcome. J Am Coll Cardiol 2011; 58:402.
  36. Pislaru SV, Pellikka PA. The spectrum of low-output low-gradient aortic stenosis with normal ejection fraction. Heart 2016; 102:665.