Low flow, low gradient aortic stenosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2] Usama Talib, BSc, MD [3]

Synonyms and keywords: Low flow low gradient aortic stenosis, LF-LG aortic stenosis, low flow low gradient aortic stenosis with low ejection fraction, low flow flow gradient aortic stenosis with normal ejection fraction

Overview

In aortic stenosis, as the aortic orifice area decreases the transvalvular gradient increases; in fact, when the aortic valve effective orifice area decreases below 1 cm2 the mean transvalvular gradient is expected to be greater than 40 mmHg.[1][2]The transvalvular gradient is highly dependent on the flow of blood through the valve; however, when severe systolic and/or diastolic myocardial dysfunction coexist with the aortic stenosis, there is a decrease in the flow through the valve leading to a prominent decrease in the transvalvular gradient, a condition referred to as low flow, low gradient aortic stenosis (LF-LG AS). LF-LG AS is a challenging diagnosis that must be done in order to tailor the management plan. It is important to recognize this entity because it might lead to either underestimation or overestimation of the degree of severity of the aortic stenosis. Two various scenarios occur in the setting of LF-LG AS depending on the status of the left ventricular ejection fraction (LVEF): LF-LG AS with low LVEF and LF-LG AS with normal LVEF.[3]

Epidemiology

Low flow low gradient aortic stenosis with low ejection fraction is reported in approximately 5 to 10% of patients with severe aortic stenosis; whereas low flow low gradient aortic stenosis with normal left ventricular ejection fraction is observed in 10 to 25% of patients with severe aortic stenosis.[4][5]

Pathophysiology

Low Flow, Low Gradient Aortic Stenosis with Low Ejection Fraction

  • When ventricular systolic dysfunction is present, the myocardium can not contract strongly enough to pump blood with a lot of pressure. In this case, low flow and subsequent low transvalvular gradient are present and this entity is referred to as LF-LG AS with low LVEF.
  • LF-LG AS with low LVEF is defined as:[1][2][3]
  1. An aortic valve areas < 1.0 cm2, and
  2. A left ventricular ejection fraction < 40-50%( 30% in other references),[4] and
  3. A mean pressure difference or gradient across the aortic valve of < 40 mm Hg
  • When low flow low gradient aortic stenosis is present, the challenge is to determine whether the LF-LG AS with low LVEF is a true severe aortic stenosis or a pseudo-severe aortic stenosis. It is very important to differentiate these two entities as they have different outcomes following aortic valve replacement.[3]
True severe aortic stenosis:
  • In true severe aortic stenosis, the aortic stenosis is so severe that it caused secondary left ventricular dysfunction. This systolic dysfunction causes decreased contractility leading to decreased ejection force and low transvalvular flow and gradient.[3]
Pseudo-severe aortic stenosis:

Following are the features of Pseudo-severe Aortic Stenosis.[3][6][7][8][9][10]

  • In pseudo-severe aortic stenosis, the aortic stenosis is mild or moderate and it co-exists with another myocardial disease that is independent from the aortic stenosis. Overestimation of the severity of the aortic stenosis may happen in this context.
  • The presence of fibrosis in the left ventricle may cause an incomplete recovery after aortic valve replacement.[11]
  • This scenario can also occur among patients in whom there is a history of myocardial infarction and insufficient contractility to mount an aortic gradient.
  • It may also occur when myocardial fibrosis develops due to longstanding aortic stenosis.


Low Flow, Low Gradient Aortic Stenosis with Normal Ejection Fraction

LF-LG AS with normal ejection fraction has been recently described.[3][12][13][14]

  • LF-LG aortic stenosis with normal LVEF is usually an advanced stage of valvular and myocardial diseases. The normal ejection fraction might lead to an underestimation of the severity of the aortic stenosis.
  • LF-LG AS with normal ejection fraction has a lot of similarities with normal ejection fraction diastolic heart failure. In fact, it is usually present in older females and in the context of hypertension. The underlying pathophysiology of LF-LG AS with normal ejection fraction is a restrictive myocardium.
  • LF-LG AS with normal ejection fraction is characterized by the presence of extensive remodeling due to predominant diastolic dysfunction as well as systolic dysfunction. However, the decrease in the systolic performance of the left ventricle does not contribute to a decrease in the ejection fraction.


Shown below is a table depicting the differences between LF-LG AS with low LVEF and LF-LG AS with normal LVEF.
LF-LG AS Percentage of the Cases of Severe AS Caused by LF-LG AS Pathophysiology Diagnostic Challenges
LF-LG AS with low LVEF 5-10% of severe aortic stenosis Decreased systolic function

-Dilated left ventricle

-Decreased contractility

Differentiation between severe aortic stenosis and pseudo-severe aortic stenosis
LF-LG AS with normal LVEF 10-25% of severe aortic stenosis Decreased diastolic function

-Small left ventricle

-Decreased compliance

Underestimation of the severity of aortic stenosis

Confounding measurement errors and small ventricle body size

Diagnosis

Low Dose Dobutamine Stress Echocardiography

  • Low dose (<20 microgram/Kg/min) dobutamine stress echocardiography allows:[6][9]
    • The differentiation between severe and pseudo-severe low flow low gradient aortic stenosis through the degree of change of both the effective orifice area and the transvalvular gradient after dobutamine infusion. Changes following dobutamine infusion are due to the fact that dobutamine causes increase in the flow across the aortic valve.
      • In pseudosevere aortic stenosis, there is increase in the effective orifice area of the aortic valve, in a way that it is larger than 1.2 cm2, and slight increase in the gradient, in a way that is inferior to 40 mmHg.
      • In severe aortic stenosis, there is absence or little increase in the effective orifice area of the aortic valve, in a way that is inferior to 1.2 cm2, and increase in the gradient to become greater than 40 mmHg.
    • The assessment of the presence or absence of left ventricular flow reserve through the degree of change in stroke volume following dobutamine infusion.
      • Left ventricular flow reserve is an indicator of operative mortality. Left ventricle flow reserve does not predict recovery of left ventricle after aortic valve replacement nor the resolution of symptoms.[3]
      • The aortic valve area should increase to more than 1-1.2 cm2 with a dobutamine infusion and the mean pressure gradient should rise above 30 mm Hg. While early surgical mortality is 32-33% in patients who fail to to achieve these improvements with dobutamine infusions, it is only 5–7% in patients who demonstrate an increase in their contractility and gradient. Five years survival after surgery was 88% in patients with improved contractility and only 10–25% in patients with unimproved contractility.
Shown below is an algorithm summarizing the interpretation of the results of low dose dobutamine stress echocardiography in the evaluation of low flow, low gradient aortic stenosis.[3]

Abbreviations: EOA: Effective orifice area; ΔPmean: mean pressure gradient

 
 
Ultrasound evaluation of aortic stenosis
Effective orifice area (EOA)≤ 1 cm2
Pressure gradient (ΔP)<40 mmHg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low grade low flow aortic stenosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal left ventricular ejection fraction
 
Left ventricular ejection fraction≤ 40-50%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dobutamine stress test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Increase in stroke volume by ≥ 20%
 
Increase in stroke volume by <20%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Presence of left ventricular flow reserve
 
Absence of left ventricular flow reserve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ΔP≥40
EOA<1-1.2
 
ΔP<40
EOA≥1-1.2
 
EOA<1-1.2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
True severe aortic stenosis
 
Pseudo-severe aortic stenosis
 
True severe aortic stenosis


Treatment

Surgical and Medical Treatment

Aortic valve replacement is the treatment of choice for aortic stenosis.[15][16]Given the associated operative risks with aortic valve replacement (AVR), true severe low flow low gradient aortic stenosis must be differentiated from pseudoaortic stenosis as the former benefit from AVR and the latter does not necessarily benefit from AVR. In addition, in case of low flow low gradient aortic stenosis with low ejection fraction, the presence or absence of reserve flow dictates the treatment plan as the operative mortality increases in the absence of reserve flow. As low flow low gradient aortic stenosis with normal ejection fraction is a newly described entity, there is no yet clear recommendations for the management.[17][18][19]

Shown below is an algorithm of the management of low flow, low gradient aortic stenosis.[3]

Abbreviations: AVR: Aortic valve replacement; EOA: Effective orifice area; ΔPmean: mean pressure gradient

 
 
Low grade low flow aortic stenosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal left ventricular ejection fraction
 
Left ventricular ejection fraction≤ 40-50%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No specific recommendations:
- Surgical AVR, or
- Transcather AVR, or
- Medical treatment
 
 
 
 
 
 
 
 
 
 
 
Dobutamine stress test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Increase in stroke volume by ≥ 20%
 
Increase in stroke volume by <20%
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ΔP≥40
EOA<1-1.2
 
ΔP<40
EOA≥1-1.2
 
EOA<1-1.2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
True severe aortic stenosis
 
Pseudo-severe aortic stenosis
 
True severe aortic stenosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical AVR
with/without CABG
 
Medical treatment
Close follow up
 
Transcather AVR


Operative Mortality Risk Factors

The risk factors for operative mortality in the case of low flow, low gradient aortic stenosis with low ventricle ejection fraction are:[4][20]

ACC/AHA Guidelines[1]

Dobutamine Stress Echocardiography

Class IIa
"1.Dobutamine stress echocardiography is reasonable to evaluate patients with low-flow/low-gradient aortic stenosis and left ventricular dysfunction.(Level of Evidence: B) "
"2.Cardiac catheterization for hemodynamic measurements with infusion of dobutamine can be useful for evaluation of patients with low-flow/low-gradient aortic stenosis and left ventricular dysfunction. (Level of Evidence: C) "

References

  1. ↑ 1.0 1.1 1.2 Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD; et al. (2008). "2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". J Am Coll Cardiol. 52 (13): e1–142. doi:10.1016/j.jacc.2008.05.007. PMID 18848134.
  2. ↑ 2.0 2.1 Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H; et al. (2013). "[Guidelines on the management of valvular heart disease (version 2012). The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)]". G Ital Cardiol (Rome). 14 (3): 167–214. doi:10.1714/1234.13659. PMID 23474606.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 Pibarot P, Dumesnil JG (2012). "Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction". J Am Coll Cardiol. 60 (19): 1845–53. doi:10.1016/j.jacc.2012.06.051. PMID 23062546.
  4. ↑ 4.0 4.1 4.2 Connolly HM, Oh JK, Schaff HV, Roger VL, Osborn SL, Hodge DO; et al. (2000). "Severe aortic stenosis with low transvalvular gradient and severe left ventricular dysfunction:result of aortic valve replacement in 52 patients". Circulation. 101 (16): 1940–6. PMID 10779460.
  5. ↑ Kulik A, Burwash IG, Kapila V, Mesana TG, Ruel M (2006). "Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch". Circulation. 114 (1 Suppl): I553–8. doi:10.1161/CIRCULATIONAHA.105.001180. PMID 16820636.
  6. ↑ 6.0 6.1 deFilippi CR, Willett DL, Brickner ME, Appleton CP, Yancy CW, Eichhorn EJ; et al. (1995). "Usefulness of dobutamine echocardiography in distinguishing severe from nonsevere valvular aortic stenosis in patients with depressed left ventricular function and low transvalvular gradients". Am J Cardiol. 75 (2): 191–4. PMID 7810504.
  7. ↑ Schwammenthal E, Vered Z, Moshkowitz Y, Rabinowitz B, Ziskind Z, Smolinski AK; et al. (2001). "Dobutamine echocardiography in patients with aortic stenosis and left ventricular dysfunction: predicting outcome as a function of management strategy". Chest. 119 (6): 1766–77. PMID 11399704.
  8. ↑ 8.0 8.1 Monin JL, Quéré JP, Monchi M, Petit H, Baleynaud S, Chauvel C; et al. (2003). "Low-gradient aortic stenosis: operative risk stratification and predictors for long-term outcome: a multicenter study using dobutamine stress hemodynamics". Circulation. 108 (3): 319–24. doi:10.1161/01.CIR.0000079171.43055.46. PMID 12835219.
  9. ↑ 9.0 9.1 Nishimura RA, Grantham JA, Connolly HM, Schaff HV, Higano ST, Holmes DR (2002). "Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine challenge in the catheterization laboratory". Circulation. 106 (7): 809–13. PMID 12176952.
  10. ↑ Zuppiroli A, Mori F, Olivotto I, Castelli G, Favilli S, Dolara A (2003). "Therapeutic implications of contractile reserve elicited by dobutamine echocardiography in symptomatic, low-gradient aortic stenosis". Ital Heart J. 4 (4): 264–70. PMID 12784780.
  11. ↑ Carabello BA, Green LH, Grossman W, Cohn LH, Koster JK, Collins JJ (1980). [[]]: 42–8 http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=7379284. Retrieved 2012-04-10. Unknown parameter |month= ignored (help); Missing or empty |title= (help)
  12. ↑ Hachicha Z, Dumesnil JG, Bogaty P, Pibarot P (2007). "Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival". Circulation. 115 (22): 2856–64. doi:10.1161/CIRCULATIONAHA.106.668681. PMID 17533183.
  13. ↑ Cramariuc D, Cioffi G, Rieck AE, Devereux RB, Staal EM, Ray S; et al. (2009). "Low-flow aortic stenosis in asymptomatic patients: valvular-arterial impedance and systolic function from the SEAS Substudy". JACC Cardiovasc Imaging. 2 (4): 390–9. doi:10.1016/j.jcmg.2008.12.021. PMID 19580719.
  14. ↑ 14.0 14.1 Lancellotti P, Magne J, Donal E, Davin L, O'Connor K, Rosca M; et al. (2012). "Clinical outcome in asymptomatic severe aortic stenosis: insights from the new proposed aortic stenosis grading classification". J Am Coll Cardiol. 59 (3): 235–43. doi:10.1016/j.jacc.2011.08.072. PMID 22240128.
  15. ↑ Pai RG, Varadarajan P, Razzouk A (2008). "Survival benefit of aortic valve replacement in patients with severe aortic stenosis with low ejection fraction and low gradient with normal ejection fraction". Ann Thorac Surg. 86 (6): 1781–9. doi:10.1016/j.athoracsur.2008.08.008. PMID 19021976.
  16. ↑ Tarantini G, Covolo E, Razzolini R, Bilato C, Frigo AC, Napodano M; et al. (2011). "Valve replacement for severe aortic stenosis with low transvalvular gradient and left ventricular ejection fraction exceeding 0.50". Ann Thorac Surg. 91 (6): 1808–15. doi:10.1016/j.athoracsur.2011.02.057. PMID 21619977.
  17. ↑ Hachicha Z, Dumesnil JG, Pibarot P (2009). "Usefulness of the valvuloarterial impedance to predict adverse outcome in asymptomatic aortic stenosis". J Am Coll Cardiol. 54 (11): 1003–11. doi:10.1016/j.jacc.2009.04.079. PMID 19729117.
  18. ↑ Malouf J, Le Tourneau T, Pellikka P, Sundt TM, Scott C, Schaff HV; et al. (2012). "Aortic valve stenosis in community medical practice: determinants of outcome and implications for aortic valve replacement". J Thorac Cardiovasc Surg. 144 (6): 1421–7. doi:10.1016/j.jtcvs.2011.09.075. PMID 22336754.
  19. ↑ Belkin RN, Khalique O, Aronow WS, Ahn C, Sharma M (2011). "Outcomes and survival with aortic valve replacement compared with medical therapy in patients with low-, moderate-, and severe-gradient severe aortic stenosis and normal left ventricular ejection fraction". Echocardiography. 28 (4): 378–87. doi:10.1111/j.1540-8175.2010.01372.x. PMID 21323995.
  20. ↑ Vaquette B, Corbineau H, Laurent M, Lelong B, Langanay T, de Place C; et al. (2005). "Valve replacement in patients with critical aortic stenosis and depressed left ventricular function: predictors of operative risk, left ventricular function recovery, and long term outcome". Heart. 91 (10): 1324–9. doi:10.1136/hrt.2004.044099. PMC 1769144. PMID 16162627.
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