Low-gradient severe aortic stenosis with normal LVEF: A disturbing clinical entity

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1 Low-gradient severe aortic stenosis with normal LVEF: A disturbing clinical entity Jean-Luc MONIN, MD, PhD Henri Mondor University Hospital Créteil, FRANCE Disclosures : None

2 77-year-old woman, mild dyspnea Body surface area = 1.77 m 2 LV ejection fraction = 60% (concentric hypertrophy) Aortic valve area = 0.9 cm 2 (0.5 cm 2 /m 2 ) Peak aortic jet velocity = 3.6 m/s Mean transaortic pressure gradient = 34 mm Hg Severe AS (AVA) with Low Gradient despite preserved LVEF : How should this patient be treated?

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4 Paradoxical Low-Flow/ Low-Gradient AS patients (retrospective): AVA i 0.6 cm 2 /m 2, LVEF > 50% - Normal Flow (SVI > 35 ml/m 2 ) in 331 patients (65%) - Paradoxical Low Flow (SVI 35 ml/m 2 ) in 181 (35%) 4 Hachicha et al. Circulation. 2007;115:

5 Paradoxical Low-Flow/ Low-Gradient AS PLF : overall survival is impaired, compared with NF patients 5 Hachicha et al. Circulation. 2007;115:

6 Paradoxical Low-Flow/ Low-Gradient AS PLF : markedly lower survival if medically treated, as compared with those who underwent AVR 6 Hachicha et al. Circulation. 2007;115:

7 Henri Mondor Paradoxical Low-flow/ Low-gradient AS : Author s conclusions - Important proportion (35%) of patients with severe AS have Low-Flow / Low-Gradients despite preserved LVEF - Pattern associated with higher global LV afterload, severe LV concentric remodeling and lower survival, which suggests a more advanced stage of disease - This condition may often be misdiagnosed, which leads to underestimation of symptoms and inappropriate delay of surgery. Hachicha et al. Circulation. 2007;115:

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9 Current echocardiographic criteria for the grading of AS Mild Moderate Severe AS Peak V < 3.0 m/s m/s > 4.0 m/s Mean PG < 25 mm Hg mm Hg > 40 mm Hg AVA > 1.5 cm² cm² < 1.0 cm² Indexed AVA / / < 0.6 cm²/m² 9 ACC/ AHA Guidelines. J. Am. Coll. Cardiol. 2006;48: e1-148

10 Inconsistencies of echocardiographic criteria for the grading of AS Consistency of 3 criteria (AVA, Gradient, V max ) / Grading of AS - Analysis of 3483 Echo studies patients, normal LV systolic function and AVA < 2.0 cm 2 - Gradient plotted vs. AVA (Gorlin formula) - Predicted curve: assuming CO = 6,0 L/min, HR = 80 bpm and SEP = 0.33 S Fitted curve : Actual data pairs 10 Minners et al. Eur Heart J. 2008;29:1043-8

11 Inconsistencies of echocardiographic criteria for the grading of AS - Peak Aortic-jet velocity is plotted vs. AVA (Continuity Equation) - Predicted curve: assuming standard LVOT diameter = 20 mm and LVOT peak velocity = 1,0 m/s - Fitted curve : Actual data pairs Minners et al. Eur Heart J. 2008;29:1043-8

12 Inconsistencies of echocardiographic criteria for the grading of AS Possible overestimation of AS severity according to AVA criteria Study limitation: no outcome data to support a revision of the criteria for AS severity Minners et al. Eur Heart J. 2008;29:1043-8

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14 Paradoxical Low-Flow/ Low-Gradient AS Variable Normal Flow (n= 331) Paradoxical Low Flow (n= 181) P value Adjusted P value MPG, mmhg 40±15 32±17 <0.001 <0.001 Body surf. area, m 2 1.8± ±0.2 NS NS LVOT diameter, mm 22±2 20±2 < Stroke Volume, ml 79±14 56±10 <0.001 NA Index AVA, cm 2/ m ± ±0.11 <0.001 NS ZVA, mmhg/ml/m 2 4.1± ±1.3 <0.001 < Hachicha et al. Circulation. 2007;115:

15 Henri Mondor The critical issue of LVOT diameter measurement Underestimation of LVOT diameter is 1 Error leading to underestimation of AVA May also lead to underestimate stroke volume and to the false conclusion of Low-Flow LVOT diameter should be re-checked (several times) on closer examination Current values: 20±2 mm (women) and 22±3 mm (men) ** TEE may be useful in case of poor image quality N. Jander. Eur Heart J. 2008; 10 (Suppl E): E11-15 ** European Registry on LGAS. Unpublished 15

16 Underestimated LVOT diameter leads to overestimation of AS severity 16 AVA = 0.9 cm 2 AVA = 1.2 cm 2

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18 Paradoxical Low-Flow/ Low-Gradient AS The signs of AS severity (i.e. high pressure gradients) can be masked by the presence of concomitant hypertension, particularly if associated with a significant decrease in systemic arterial compliance Blood pressure may be pseudo normalized in patients with high hemodynamic load and low stroke volume Dumesnil et al. Eur Heart J. 2010; 31 : 281-9

19 Systemic pressure does not directly affect MPG and AVA estimates in AS In vitro model of AS, AVA = 1.0 cm 2, constant flow rate = 2.0 L/min: Systolic pressure = 80 mmhg Systolic pressure = 80 mmhg Systolic pressure = 200 mmhg Systolic pressure = 200 mmhg Computed modeling of velocity (left) and absolute pressure (right) Mascherbauer et al. Eur Heart J. 2008;29:

20 Systemic pressure does not directly affect MPG and AVA estimates in AS In vitro model of AS, AVA = 1.0 cm 2, constant flow rate = 2.0 L/min: Blood pressure itself does not directly affect pressure gradients in AS. Low gradient is most likely due impaired LV systolic function (afterload mismatch) with decrease in stroke volume Mascherbauer et al. Eur Heart J. 2008;29:

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22 77-year-old woman, AS / mild dyspnea

23 LVEF = 60% (Biplane Simpson)

24 Speckle tracking : longitudinal strain Global longitudinal strain is markedly decreased (-12%) : normal values -20%

25 LVEF of 50% may represent systolic dysfunction in the setting of severe AS with concentric hypertrophy in this case, Low-flow is neither unexpected nor paradoxical N. Jander. Eur Heart J. 2008; 10 (Suppl E): E11-15

26 Paradoxical Low-flow AS : Impairment of intrinsic LV function 120 consecutive Pts, index AVA <0.6 cm 2 /m 2 and LVEF> 50%, 2D-Strain analysis Patients with PLF have impaired LV myocardial function evidenced by speckle tracking imaging Mielot et al. Eur Heart J. 2009; 30 (Abstract Suppl ): 683

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28 Comprehensive evaluation of aortic stenosis severity - Systemic arterial compliance - systemic vascular resistance - valvulo-arterial impedance - LVEF (Simpson + Dumesnil) - Mid-wall fractional shortening This will add little time to the examination (?) Peripheral blood pressure should be recorded in every patient Dumesnil et al. Eur Heart J. 2010; 31 : 281-9

29 Valvulo-arterial Impedance (Zva): Do we need a new Concept? Clinical implications - Zva does not account separately for the valvular vs. arterial component of LV afterload - Therefore, High Zva may reflect either: 1/ Moderate AS with severe hypertension, requiring Blood pressure control 2/ Truly severe AS requiring valve replacement - In current practice, we can still rely on simple measures of AS severity (peak velocity, gradient, AVA), as long as we also consider blood pressure and cardiac output H. Baumgartner & CM. Otto. J Am Coll Cardiol. 2009;54:

30 Assessment of valve calcification by TTE : Look at the valve! 1/ No calcification 2/ Mildly calcified (isolated, small spots), 3/ Moderately calcified (multiple bigger spots) 4/ Heavily calcified (extensive thickening/ calcification of all cusps). Rosenhek et al. N Engl J Med. 2000;343:611

31 Incremental value of serum BNP over peak aortic-jet velocity Prospective study, 211 asymptomatic patients (72 years [63-77]) with moderate / severe AS Gender Age, years Peak Velocity, m/s Serum BNP, pg/ml Risk Score FU Duration, Months Cause of Death Male (Q3) 9 CHF Male (Q3) 6 Pulmonary Edema Female (Q4) 19 Sudden death 31 Monin et al. Circulation. 2009; 120: 69-75

32 77-year-old woman, mild dyspnea LV ejection fraction = 60% Global longitudinal strain = - 11% Aortic valve area = 0.9 cm 2 (0.5 cm 2 /m 2 ) Mean transaortic pressure gradient = 34 mm Hg Severe aortic valve calcification BNP = 450 pg/ ml Valve replacement was performed Uncomplicated course thereafter

33 Take-Home messages Some cases of Low-Flow / Low-gradient AS may be due to: - Underestimation of LVOT diameter, leading to underestimation of stroke volume and AVA - Inconsistencies of current criteria for defining AS severity The prevalence of this clinical entity may not be as high as 30% (probably less than 10%) Uncontrolled hypertension participates in global LV overload and thus, should be adequately treated

34 Take-Home messages Low-flow/ Low-gradient AS with preserved LVEF is due to intrinsic myocardial dysfunction, as evidenced by Speckle Tracking imaging Valvulo-arterial impedance is unable to differentiate the respective burden of aortic stenosis vs. arterial load Valve calcification and serum BNP may be helpful for clinical decision making

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