Validation of Conventional and Simplified Methods to Calculate Projected Valve Area at Normal Flow Rate in Patients With Low Flow, Low Gradient Aortic Stenosis: The Multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) Study




Background


It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal transvalvular flow rate (AVA proj ), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVA proj in a large series of patients and to propose a new clinically applicable simplified method to estimate AVA proj .


Methods


AVA proj was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVA proj = AVA rest + slope × (250 − Q rest ). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q.


Results


There was a strong correlation between AVA proj calculated by the two methods ( r = 0.95, P < .0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVA proj demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVA proj ≤ 1 cm 2 , 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVA proj correlated well with valve weight ( r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVA proj ≤ 1.2 cm 2 (hazard ratio, 1.65; P = .02) and simplified AVA proj ≤ 1.2 cm 2 (hazard ratio, 2.70; P < .0001) were independent predictors of mortality. Traditional dobutamine stress echocardiographic indices were not predictive.


Conclusion


In patients with low-flow AS, AVA proj better predicts underlying AS severity and patient outcomes than traditional dobutamine stress echocardiographic indices. Simplified AVA proj is easier to calculate than conventional AVA proj , facilitating the use of AVA proj in clinical practice.


Patients with left ventricular (LV) dysfunction and low-flow, low-gradient severe aortic stenosis (AS) have a poor prognosis with conservative therapy but potentially high operative mortality if treated surgically. Identifying which patients are likely to benefit from surgical intervention can be a diagnostic challenge. In the setting of a low-flow state, it is often difficult to separate patients with true severe (TS) AS and concomitant LV systolic dysfunction from those with pseudosevere (PS) AS (ie, with incomplete opening of the valve because of poor LV function). Yet this distinction is essential because patients with TS AS and poor LV function will generally benefit from aortic valve replacement (AVR), whereas those with PS AS may not benefit from surgical intervention.


Changes in aortic valve area (AVA) and gradient during low-dose dobutamine infusion may be helpful in differentiating TS from PS AS. Generally, dobutamine-induced increases in transvalvular flow (Q) will result in increases in AVA in patients with PS AS because of the preservation of aortic cusp mobility, whereas there are no or minimal increases in AVA and marked increases in transvalvular gradient in patients with TS AS. However, the changes in gradient and AVA during stress depend largely on the magnitude of flow augmentation achieved during dobutamine stress echocardiography (DSE), which may vary considerably from one patient to another. To overcome this important limitation, we proposed a new index of AS severity derived from DSE, the projected AVA at a normal Q rate (AVA proj ), and demonstrated that this index was superior to traditional Doppler echocardiographic indices for differentiating TS from PS AS. However, the calculation of AVA proj is somewhat complex, requiring the calculation of Q and AVA at rest and at several different dobutamine infusion rates, potentially limiting its application to the clinical setting. The objectives of this study were (1) to prospectively validate the diagnostic and prognostic performance of AVA proj in a large series of patients with low-flow, low-gradient AS and (2) to propose a new simplified method to estimate AVA proj that can be easily incorporated into clinical practice.


Methods


The protocol of the True or Pseudo Severe Aortic Stenosis (TOPAS) multicenter prospective observational study was described in detail in our previous publications. Briefly, between July 2002 and March 2008, we recruited 142 patients with low-flow, low-gradient AS, defined as AVA ≤ 1.2 cm 2 , indexed AVA ≤ 0.6 cm 2 /m 2 , a mean transvalvular gradient ≤ 40 mmHg, and an LV ejection fraction ≤ 40%. All patients underwent DSE using commercially available ultrasound systems, and functional capacity was assessed using the Duke activity status index. The dobutamine infusion protocol consisted of 8-minute increments of 2.5 to 5 μg/kg/min up to a maximum dose of 20 μg/kg/min. The AVA and gradients were measured at rest and at each stage of DSE. AVA proj was calculated using two methods, as follows.


Conventional Method


For each patient, AVA was plotted against Q at each dobutamine stage, and AVA at a standardized flow rate of 250 ml/s was projected from the equation using the regression line fitted to the plot of AVA versus Q ( Figure 1 ):


<SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='AVAproj=AVArest+VC×(250&amp;−Qrest),’>AVAproj=AVArest+VC×(250&Qrest),AVAproj=AVArest+VC×(250&−Qrest),
AVA proj = AVA rest + VC × ( 250 & − Q rest ) ,
where AVA rest and Q rest are AVA and Q at rest, and VC is the valve compliance, or slope of the regression line. Mean Q was calculated by dividing stroke volume by LV ejection time ( Figure 2 ). Stroke volume was measured using pulsed-wave Doppler in the LV outflow tract (LVOT). LVOT diameter was measured at rest, and the same diameter was used for the calculation of stroke volume during DSE.


Figure 1


Calculation of conventional and simplified AVA proj in a patient with low-flow AS. VC simpl is derived from ΔAVA and ΔQ, the maximum absolute increases in AVA and flow, respectively, during dobutamine infusion.



Figure 2


Doppler echocardiographic image acquisition and measurements required to calculate simplified AVA proj in (A) a patient with TS AS and (B) a patient with PS AS. Stroke volume (SV) is calculated by multiplying LVOT cross-sectional area by the LVOT velocity-time integral (VTI) obtained by pulsed-wave Doppler. Mean Q is computed by dividing SV by LV ejection time (LVET). AVA is calculated by dividing SV by the aortic jet (Ao) VTI obtained by continuous-wave Doppler. The LVOT diameter (LVOTd) is assumed to remain constant during DSE. These measurements and calculations are performed at rest and at peak stress. Simplified AVA proj can then be calculated from these measurements by using first equation 2 and then equation 1 . ΔP , mean transvalvular gradient.


Simplified Method


In the simplified method, the slope of the regression line (VC simpl ) was estimated by dividing the increase in AVA from rest to peak dobutamine dose by the increase in Q from rest to peak dobutamine dose ( Figures 1 and 2 ).


<SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='VCsimpl=AVApeak−AVArestQpeak−Qrest,’>VCsimpl=AVApeakAVArestQpeakQrest,VCsimpl=AVApeak−AVArestQpeak−Qrest,
VC simpl = AVA peak − AVA rest Q peak − Q rest ,

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Jun 16, 2018 | Posted by in CARDIOLOGY | Comments Off on Validation of Conventional and Simplified Methods to Calculate Projected Valve Area at Normal Flow Rate in Patients With Low Flow, Low Gradient Aortic Stenosis: The Multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) Study

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