a Department of Cardiology, Vienna General Hospital, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria
b Department of Bioengineering, Vienna General Hospital, University of Vienna, Vienna, Austria
c Department of Cardiothoracic Surgery, Vienna General Hospital, University of Vienna, Vienna, Austria
d Ludwig Bolzmann Institutes of Cardiovascular and Cardiosurgical Research, Vienna, Austria
Received October 26, 2003;
revised January 14, 2004;
accepted February 13, 2004
* Corresponding author. Tel.: +43-1-40-400-4614; fax: +43-1-408-11-48
E-mail address: helmut.baumgartner{at}univie.ac.at
Abstract
Background The calculation of valve resistance rather than aortic valve area (AVA) has been proposed for the assessment of aortic stenosis (AS), based on the claim that it is less flow-dependent. Even more importantly, valve resistance has been reported to distinguish between truly severe and "pseudosevere" AS in patients with low cardiac output. However, the diagnostic value of valve resistance remains controversial.
Methods and results Models of stenotic aortic valves (plates and nozzles) and biological stenotic valves were studied in a pulsatile in vitro circuit using Doppler ultrasound and direct pressure and flow measurements. Anatomic AVAs ranged from 0.5 to 1.25 cm2; cardiac output varied from 1.8 to 9.0 l/min. Effective AVA was calculated with the continuity equation. The orifices of the biological valves were recorded with a video camera for planimetry. In low flowlow gradient AS, truly severe stenosis was defined by an AVA remaining 0.85 cm2 after flow normalisation, whereas AVA increased beyond 0.85 cm2 in pseudosevere AS.
In rigid stenoses, valve resistance increased significantly with flow, while in bioprostheses this flow dependence was partially masked by an actual increase of the anatomic orifice area. In low flowlow gradient AS, valve resistance was significantly smaller in pseudosevere AS compared to truly severe AS (129±28 vs. 176±33 dynescm5; ) at a similar baseline effective AVA. After the exclusion of datasets with mean gradients
15 and
35 mmHg, the difference in valve resistance between truly severe and pseudosevere AS was no longer significant (162±26 vs. 141±22 dynescm5;
). Nevertheless, valve resistance
120 dynescm5 was found only in pseudosevere stenoses while valve resistance
180 dynescm5 marked truly severe stenosis.
Conclusions Valve resistance is flow-dependent and not superior to calculated AVA for the assessment of AS. In low flowlow gradient AS, valve resistance 120 dynescm5 identifies pseudosevere AS, whereas valve resistance
180 dynescm5 implies truly severe AS. However, values between 120 and 180 dynescm5 are nondiagnostic, requiring repeated AVA calculations after flow normalisation.
Key Words: Valve resistance Aortic stenosis Haemodynamics
Introduction
It is still uncertain whether valve resistance provides important information beyond gradient and valve area in the assessment of aortic stenosis (AS), especially in low flowlow gradient aortic stenosis (AS). Its calculation has been proposed for the following reasons:
However, it has recently been questioned that valve resistance is less flow-dependent than AVA.69 Furthermore, it remains unclear whether valve resistance can indeed separate truly severe from pseudosevere AS under low-flow conditions.9,10 Selection bias, small patient numbers, and the lack of an adequate standard of reference limit the usefulness of clinical studies in clarifying these questions. Furthermore, studies that include all modalities of AS assessment in addition to valve resistance calculations (gradients, effective AVA, and true anatomic orifice area by planimetry) are not available.
The present in vitro study assesses various types and degrees of AS by Doppler and catheter technique for known anatomic orifice areas. In this well-controlled setting, we studied the flow dependence of valve resistance and its value for distinguishing between truly severe and pseudosevere AS in the setting of low flowlow gradient AS.
Methods
In vitro flow model
The modular in vitro flow circuit used in this study has been described previously in detail11 (Fig. 1). The system is driven by a computer-controlled piston pump (Vivitro Inc.TM) that generates stroke volumes of 10100 ml. Ejection pressure can range from 0 to 300 mmHg, pulse rate from 30 to 120 beats per minute, and ejection time from 100 to 700 ms. Flow rate is measured with an ultrasonic flowmeter (Transonic Systems Inc.TM) that was calibrated against timed collections. In the present study, the flow probe was placed between the pump and stenosis. Pressure taps 10 mm proximal and 50 mm distal to the stenosis were connected to electronic pressure transducers (Peter van BergTM, Hellige signal amplifierTM) by means of fluid-filled catheters. We maintained physiologic pressures by adjusting pump characteristics, distal compliance, and resistance. An aortic diameter of 4.0 cm was chosen to minimise pressure recovery.12 A mechanical valve (Carbomedics 25 mm) between the ventricle and test section prevented backflow when plates with circular orifices or nozzles served as models of stenotic valves. The test section has been designed to allow optimal alignment of the Doppler beam and flow across the stenosis. To mount bioprostheses in the circuit, they were sutured into silicon rings that were fixed on Plexiglas rings. Imaging of the cusp motion of bioprosthetic valves was performed from an axial window with a high-speed video camera (Kodak EktaproTM).
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Doppler, pressure, and flow tracings were simultaneously recorded and transferred to a data acquisition system (Hellige GmbHTM, PCTM) for further analysis, which was performed with commercially available software (Famos 3.0TM).
The setup utilised resulted in Doppler, flow, and pressure tracings very similar to the in vivo setting.
Types of stenoses
Lucite plates (2-mm thickness) with central circular orifices of 0.5, 0.75, 1.0, and 1.25 cm2 served as models of rigid discrete stenoses. In addition, gradually tapering nozzles with a length of 0.7 cm, inflow angle of 45°, and orifice areas of 0.5, 0.75, 1.0, and 1.25 cm2 were used to emulate doming valves with a fixed orifice.
For the assessment of potentially extensible orifices, two Carpentier Edwards 23-mm bioprostheses were used. The commissures of the bioprosthetic valves were sewed together in several steps to simulate 10 different degrees of valvular aortic stenosis (anatomic AVA 0.47 to 1.57 cm2; mean±SD 1.01±0.29 cm2). An experienced cardiac surgeon performed all procedures.
Test protocol
For every experimental setup, the driving pressure of the ventricle, outflow compliance, and outflow resistance were varied to obtain eight different flow rates while maintaining physiologic downstream pressures. Cardiac output ranged from 1.8 to 9.0 l/min. This maximum cardiac output, however, could only be achieved for the larger orifices but not for the small valve areas. Pulse rate was held constant at 60 beats/min, with an ejection time ranging from 320 to 420 ms. Directly measured pressure and flow data, Doppler echocardiographic measurements, and images of the bioprosthetic valves for orifice planimetry were collected at each flow rate.
Optical planimetry
For planimetry of the anatomic valve area, the bioprostheses were imaged with a high-speed colour video camera system (Kodak EktaproTM, up to 1000 frames/s). Cold light (DedocoolTM, up to 4 Mio lux) was used for the required illumination of the valves. Planimetry was carried out under the same haemodynamic conditions as Doppler and catheter measurements were made using the test fluid without added cornstarch. Axial videography of the bioprostheses was performed. The images were digitised and orifices at maximum opening were traced manually for planimetry.
Doppler echocardiography
A Vingmed CFM 800 (Vingmed Sound A/S) with a Duplex probe (2.5 MHz CW-Doppler) was used for continuous-wave and pulsed-wave Doppler measurements. The ultrasound probe was coupled to the model with gel (GerosonicTM) and its position was carefully adjusted to obtain the highest Doppler velocities across the stenosis. High-quality pulsed-wave Doppler tracings of the left ventricular outflow tract (LVOT) and continuous-wave Doppler transvalvular velocity (AO) tracings were collected. The systolic velocitytime integral (VTILVOT, VTIAO) was calculated using the onboard quantitation package and manual tracing. For each measurement, an average of three beats was taken. Stroke volume (SV) was calculated as
![]() | (1) |
![]() | (2) |
Valve resistance was calculated using the following equation2,7
![]() | (3) |
Effective aortic valve area (AVADoppler) was calculated using the continuity equation:7
![]() | (4) |
Calculations based on direct flow and pressure measurements
Mean transvalvular flow was determined by integrating the area under the flow curve and dividing it by the measured systolic ejection time. The mean pressure gradient
was calculated by integrating the difference between ventricular and aortic pressure throughout systole and dividing it by the ejection period. Valve resistance was obtained using Eq. .
Statistical analysis
Results are expressed as mean±standard deviation. The relationship between flow rate and valve resistance and between flow rate and valve area was assessed by linear regression analysis. Pearson correlation coefficients were calculated. Differences between groups were analysed using single-factor analysis of variance (ANOVA).
Results
The average stroke volume was 73±30 ml, ranging from 30 to 148 ml. Mean systolic pressure gradients ranged from 6 to 170 mmHg (mean±SD, 55.3±34.8 mmHg).
The valve resistance obtained from Doppler data correlated well with valve resistance based on direct flow and pressure measurements . The latter was, however, slightly but consistently higher than valve resistance by Doppler (mean difference±SD, 32.5±26.9 dynescm5) due to the slightly higher cardiac outputs calculated by Doppler. In the following analyses, only Doppler valve resistance is used.
The Reynolds numbers of the stenotic jet ranged from 2300 to 12000.
Flow dependence of resistance
Valve resistance was flow-dependent in all three types of stenosis. The steepness of the valve resistance/flow slopes was determined by the anatomic orifice area, with the greatest steepness in the smallest orifices (Fig. 2(a)).
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In nozzles, valve resistance ranged from 64 to 685 dynescm5 (mean±SD, 307±174 dynescm5). The flow-dependence of valve resistance was more pronounced than in plates, with an increase ranging from 95% to 220% (mean±SD, 135±65%; Fig. 2(a)). Effective AVA, however, changed less than in plates (mean increase±SD, 7±3%; range, 310%; , Fig. 2(b)).
In biological valves, valve resistance ranged from 63 to 375 dynescm5 (mean±SD, 150±74 dynescm5). Compared with rigid stenosis, valve resistance increased markedly less with flow (Fig. 2(a)), by only 35±20% (range, 978%). Anatomic orifice areas by optical planimetry, however, significantly increased with flow (mean % increase±SD, 35±18%, range 1566%). Accordingly, effective AVA increased by 34±12% (range, 1755%; Fig. 2(b)).
Fig. 3 illustrates the effect of orifice extensibility on the flow dependence of valve resistance. In valves with small changes in the anatomic orifice area with flow (rather rigid bioprostheses), valve resistance increased by up to almost 90%. However, in valves with a marked increase in anatomic AVA, valve resistance changed only slightly, pretending little flow dependence of this parameter.
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Group A=truly severe AS: AVA remained 0.85 cm2 at normalised flow. Mean AVA±SD was 0.63±0.03 cm2 at low flow and 0.69±0.05 cm2 at normal flow.
Group B=pseudosevere AS: continuity equation AVA increased beyond 0.85 cm2 at normal flow (mean AVA±SD 0.79±0.04 cm2 at low flow, 1.00±0.14 cm2 at normal flow).
On average, valve resistance was significantly higher in truly severe AS when compared to pseudosevere AS (129±28 vs. 176±33 dynescm5; ; Fig. 4(a)). However, there was a wide overlap between severe and pseudosevere AS that did not allow the distinction between the two entities on the basis of individual resistance values. In addition, AVA and pressure gradients were significantly different between groups (Fig. 4(b) and (c)). Thus, in a second step we restricted our analysis to valves with comparable valve areas at baseline in both groups by eliminating valves with AVA
0.7 cm2 (Fig. 5(a)(c)). Although the difference in valve resistance remained significant, the overlap increased. In addition, mean pressure gradients were again significantly different between the two groups. Therefore, in a final step we restricted the analysis to valves with comparable AVAs and comparable gradients at baseline by eliminating datasets with gradients
15 mmHg and
35 mmHg. This is also the range of gradients where the distinction between severe and pseudosevere AS is most difficult in the clinical setting. In this subset, valve resistance did not longer significantly differ between group A and B (
, Fig. 6(a)(c)).
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Discussion
Flow dependence of valve resistance
While several previous clinical studies reported valve resistance to be less flow-dependent than Gorlin as well as Doppler continuity equation-derived valve areas,15 Burwash and coworkers7 demonstrated significant flow dependence of valve resistance. These clinical results were confirmed by an in vitro study.6 In a more recent in vivo as well as in vitro investigation, Blais and coworkers9 demonstrated that valve resistance is markedly flow-dependent. Looking more closely at the mathematic formulas used to calculate effective AVA and valve resistance, can also be expressed by
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From this equation the flow dependence of valve resistance is obvious. An increase in flow must necessarily result in an increase in resistance unless it is compensated by a concomitant increase in effective AVA.9 Moreover, flow dependence must increase exponentially as the effective AVA gets smaller since the denominator of the equation is squared.
Our experimental findings are in agreement with this basic concept. Valve resistance increased with flow in both rigid models of AS and bioprostheses. In rigid stenoses the steepness of the valve resistance/flow slope was determined by the anatomic orifice area (Fig. 2(a)). Fig. 3 illustrates how the flow dependence of valve resistance is determined by changes in the anatomic orifice area. Rigid bioprosthetic valves with small changes of the anatomic valve area presented with a significant increase in valve resistance with flow. In contrast, only small changes in valve resistance were observed in extensible orifices where an increase in flow led to significant changes of the anatomic orifice area. Thus, the small or missing increase in valve resistance caused by an actual increase in valve area apparently led to the misinterpretation of previous clinical studies that valve resistance is only marginally flow-dependent.15 This has also been suggested in a recent clinical study by Burwash et al.13
Thus, valve resistance certainly has no advantages compared to AVA calculations with regard to flow dependence. The fact that valve resistance obscures actual changes in AVA with flow makes it even less useful for the evaluation of aortic stenosis.
Clinical relevance of valve resistance for the assessment of low flowlow gradient AS
In patients with a small aortic valve area but low gradient and low flow rate, it remains challenging to distinguish between truly severe AS and mild-to-moderate AS where AVA is only functionally small and potentially increases with flow (i.e., pseudosevere stenosis). Even if valve resistance is flow-dependent, it may still be useful in this setting. Cannon and coworkers3 were the first to report that valve resistance separated patients with truly severe AS from those who had only moderate disease, as demonstrated either intraoperatively or by nitroprusside testing. However, the study population was small (18 patients with severe AS and 8 with pseudosevere AS). Furthermore, the two groups were already separated by mean pressure gradients without significant overlap.
The more recent study of Roger et al.10 comprised more than 400 patients. After continuity-equation AVA and mean pressure gradient by Doppler echocardiography had been considered, valve resistance did not add more information with regard to the severity of the stenosis and operative mortality. This also remained true for patients with a mean pressure gradient 50 mmHg and a reduced cardiac index. However, the group with nonsevere disease comprised only 17 patients compared to 390 cases with truly severe AS. Furthermore, only patients who underwent surgery for aortic valve stenosis were included.
These two studies clearly demonstrate that clinical studies that tried to answer this question are definitely limited by selection bias, small patient numbers, and the lack of an accurate standard of reference.
The present in vitro study is unique in providing not only a wide spectrum of low flowlow gradient AS situations, but in allowing for Doppler measurements as well as direct flow and pressure measurements while knowing the actual anatomic AVA in each haemodynamic setting. When looking at the entire dataset, valve resistance indeed differed significantly between truly severe and pseudosevere stenoses (Fig. 4(a)). However, there was a wide overlap. Only valve resistance 180 dynescm5 appeared to identify truly severe AS whereas valve resistance
120 dynescm5 was found only in pseudosevere AS. Valve resistances below and above these cutoff values may help to rapidly distinguish the two entities. However, in the frequent settings of valve resistance ranging between 120 and 180 dynescm5, this measurement obviously remains inconclusive. Furthermore, when we eliminated datasets with gradients
15 mmHg, where truly severe AS is unlikely, and datasets with gradients
35 mmHg, where pseudosevere AS is unlikely, valve resistance was no longer significantly different between the two groups (Fig. 6). Thus, in the range of AVA and gradient data where additional information is most important for correct diagnosis, valve resistance is not helpful. Procedures that attempt to normalise flow and repeated AVA calculations appear to be indispensable in this situation.
Limitations
In vitro models cannot precisely duplicate all complex flow dynamics and valve morphologies that may be encountered in patients with aortic stenosis. The biological valves used in this study were not calcified, as is frequently the case in the clinical setting. Plexiglas plates and nozzles served as models of rigid stenosis, which is also a simplification. Nevertheless, the experimental setup closely simulated the clinical setting.
Despite some limitations, only experimental studies can provide accurate flow and pressure measurements as well as exact orifice areas and their changes with flow.
Clinical implications
Valve resistance is flow-dependent and is not superior to aortic valve area calculations for the assessment of AS severity. In low flowlow gradient AS, valve resistance 120 dynescm5 appears to identify pseudosevere AS, whereas valve resistance
180 dynescm5 implies truly severe AS. However, values between 120 and 180 dynescm5, which are very common in this setting, are not diagnostic. Thus, in most instances, procedures that attempt to normalise flow and repeated AVA calculations will be necessary for correct diagnosis.
Footnotes
Supported by a grant of the Jubiläumsfonds der Öesterreichischen Nationalbank, Otto-Wagner-Platz 3, 1011 Vienna, Austria.
References