“overestimation” of catheter gradients by doppler ultrasound in patients with aortic stenosis: a predictable manifestation of pressure recovery

Patients

The study population consisted of 23 patients who were referred for evaluation of aortic stenosis. Cardiac catheterization and Doppler echocardiography were performed within 24 h by independent investigators blinded to the results obtained by the other technique. Two patients had to be excluded, one because of inadequate Doppler quality and one because the left ventricle could not be reached at catheterization. The characteristics of the remaining 21 patients are presented in Table 1.

Cardiac catheterization

A standard procedure of left and right heart catheterization was performed including coronary angiography and left ventriculography. The left ventricle could be reached by retrograde advancement of the catheter from the aorta in all but one patient. In this patient, transseptal puncture was avoided since the clinical decision for surgery had already been made based on noninvasive data, and the patient was, therefore, excluded from the study. Left ventricular and aortic pressures were simultaneously measured using a 8F double lumen catheter (Double Lumen Pigtail; Cordis Europe, Rotterdam, the Netherlands) with a distance of 10 cm between proximal and distal holes in eight patients. In a typical catheter position, the distance between aortic valve and the proximal hole approximated 4 to 5 cm. In 13 patients careful computer-assisted catheter pullback measurements were performed with a 7F pigtail catheter (Standard Ducor; Cordis Europe) and a specially designed computer program that superimposes aortic and left ventricular pressure tracings with identical cycle length and guarantees exact timing. Aortic pressures were registered with the catheter close to the aortic valve so that the farthest distal holes could be assumed to have a distance of again approximately 4 to 5 cm to the aortic valve. Based on in vitro data (3,5,6,12), one can expect that, for clinical purposes, these measurements included most of pressure recovery. Depending on the actual hemodynamic and anatomic data in a given patient, some pressure recovery could theoretically occur even further downstream. However, the actual change in pressure could then be expected to be small and of probably no clinical relevance.

In addition to the conventional calculations of peak-to-peak and mean pressure gradients, peak catheter gradients—defined as maximal instantaneous difference between left ventricular and aortic pressure—were measured for comparison with the corresponding Doppler data. Cardiac output was measured using the Fick principle, and aortic valve areas were calculated using the Gorlin equation.

Doppler echocardiography

A Vingmed CFM 750 (Vingmed Sound A/S, Horton, Norway) equipped with a duplex probe (2.5 MHz CW-Doppler) and a pencil probe (1.9 MHz) was used. A standard examination including M-mode, two-dimensional echocardiography and conventional and color Doppler was performed. The transstenotic velocity was recorded from the apical, suprasternal, right parasternal and subcostal approaches with special care to obtain the highest velocities. Peak Doppler gradients (Δp) were calculated from the maximal instantaneous Doppler velocity across the stenosis (v) using the simplified Bernoulli equation (Δp = 4v²). Since velocities proximal to the stenosis did not exceed 1 m/s, they were neglected. Mean Doppler gradients were calculated by averaging the instantaneous Doppler gradients throughout the ejection period using the on-board quantitation package. Hand tracing of the spectral display velocity curve was used. Results were obtained by averaging the calculations of three beats.

Aortic valve area was calculated with the continuity equation using the velocity time integrals obtained across the stenosis and in the left ventricular outflow tract. The cross-sectional area of the outflow tract was calculated from its inner diameter assuming a circular shape. In addition to standard M-mode, two-dimensional echo and Doppler measurements, the inner diameter of the aorta was measured at the sinus of Valsalva, the sinotubular junction and the ascending aorta 1 cm distal to the sinotubular junction. The cross-sectional area of the aorta was calculated from the diameter assuming a circular shape.

Prediction of pressure recovery and correction of Doppler gradients

Statistical analysis

Results were expressed as mean ± standard deviation (SD). Differences between Doppler and catheter gradients and differences between observed Doppler-catheter gradient differences and predicted pressure recovery were analyzed as suggested by Bland and Altman (13). The relationship between predicted pressure recovery and observed Doppler-catheter gradient differences and the relationships between noncorrected as well as corrected Doppler gradients and catheter gradients were also assessed by linear regression analysis, and Pearson correlation coefficients were calculated.

An unpaired Student ttest was used to compare the observed Doppler-catheter gradient differences between groups of patients with >3 cm and those with ≤3 cm diameter of the aorta. This cutoff value was based on previous in vitro experience (3). Statistical significance was set at p < 0.05.

Predicted pressure recovery and differences between Doppler and catheter gradients

The predicted extent of pressure recovery and thus predicted differences between Doppler and catheter gradients ranged from 5 to 82 mm Hg (mean ± SD, 19 ± 16 mm Hg) and 3 to 54 mm Hg (12 ± 11 mm Hg) for peak and mean gradients, respectively. These predicted differences compared well with the observed differences, which ranged from −5 to 75 mm Hg (18 ± 18 mm Hg) and −7 to 48 mm Hg (11 ± 13 mm Hg) for peak and mean gradients, respectively (Figs. 1–4). ⇓⇓⇓⇓Predicted pressure recovery and observed differences between Doppler and catheter gradients correlated well (r = 0.90, y = 0.78x + 4.4, SEE = 7.0 mm Hg for peak gradient differences and r = 0.85, y = 0.70x + 4.4, SEE = 5.8 mm Hg for mean gradient differences), and mean difference between predicted pressure recovery and observed Doppler-catheter gradient differences was 0.4 ± 8.0 and 1.1 ± 6.8 mm Hg for peak and mean gradients, respectively (Figs. 3 and 4).

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Figure 1

Differences between peak Doppler and peak catheter gradients versus average peak gradient by Doppler and catheter technique. Mean difference ±2 SD are represented by the dashed lines. Data of patients with a diameter of the ascending aorta ≤3 cm are indicated by filled circles, whereas open circles represent data from patients with a diameter of the aorta >3 cm.

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Figure 2

Differences between mean Doppler and mean catheter gradients versus average mean gradient by Doppler and catheter technique. Mean difference ±2 SD are represented by the dashed lines. Data of patients with a diameter of the ascending aorta ≤3 cm are indicated by filled circles, whereas open cicles represent data from patients with a diameter of the aorta >3 cm.

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Figure 3

Differences between Doppler predicted (i.e., pressure recovery) and observed Doppler-catheter gradient differences (peak gradient) versus average peak gradient differences by prediction and observation. Mean difference ±2 SD are indicated by the dashed lines.

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Figure 4

Differences between Doppler predicted (i.e., pressure recovery) and observed Doppler-catheter gradient differences (mean gradient) versus average mean gradient differences by prediction and observation. Mean difference ±2 SD are indicated by the dashed lines.

In patients with aortas larger than 3 cm, only small differences between Doppler and catheter gradients were found, whereas the group with a diameter ≤3 cm for the aorta presented with significant differences (7.3 ± 8.7 vs. 24.8 ± 19.7 mm Hg and 2.6 ± 6.1 vs. 16.2 ± 13.2 mm Hg for peak and mean gradients, respectively; p <0.05 for both). Peak Doppler-catheter gradient differences greater than 20 mm Hg were found in seven patients, and none of these had an aorta larger than 3 cm in diameter.

Noncorrected and corrected Doppler gradients versus catheter gradients

Both the noncorrected and the corrected Doppler gradients correlated well with catheter gradients (r = 0.93–0.97). However, noncorrected Doppler gradients significantly overestimated the catheter gradients on average (slopes, 1.36 and 1.25; mean difference 18 ± 18 and 12 ± 11 mm Hg for peak and mean gradients, respectively; Figs. 5 and 6), ⇓⇓while Doppler gradients corrected for pressure recovery showed good agreement with catheter gradients (slopes, 1.03 and 0.96; Figs. 5 and 6). Mean differences (± SD) between Doppler predicted catheter gradients and observed catheter gradients were 0.4 ± 8.0 and 1.1 ± 6.8 mm Hg for peak and mean gradients, respectively (Table 2).

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Figure 5

Peak Doppler gradients (open circles)and Doppler predicted peak catheter gradients (filled circles)versus observed peak catheter gradients (dashed line= line of identity).

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Figure 6

Mean Doppler gradients (open circles)and Doppler predicted mean catheter gradients (filled circles)versus mean catheter gradients (dashed line= line of identity).

Doppler assessment of pressure gradients across aortic stenosis and the role of pressure recovery

Continuous-wave Doppler has widely been used for the estimation of pressure gradients across stenosed aortic valves, and good agreement between Doppler and catheter gradients has repeatedly been reported (7–9). However, most studies included at least some patients with marked overestimation of catheter gradients by Doppler (8,10), and consistent overestimation of catheter gradients by Doppler has been reported by some investigators (11)without offering a conclusive explanation for this observation. Recent studies have demonstrated that pressure recovery can explain apparent “overestimation” of catheter gradients by Doppler in various settings such as bileaflet prosthetic valves (5,14), coarctation of the aorta (15), hypertrophic obstructive cardiomyopathy (12,16)or fixed tunnel obstructions (17). Although pressure recovery has also been demonstrated in experimental (1,2)and in clinical studies (4)of native aortic stenosis, this phenomenon has not been recognized as a source of discrepancy between Doppler and catheter gradients across stenosed aortic valves.

We have recently shown in vitro that pressure recovery can indeed cause significant differences between Doppler and catheter gradients in aortic stenosis (3). In this in vitro model, the extent of pressure recovery and the eventual differences between Doppler and catheter gradients critically depended on the orifice velocity, the aortic valve area and the size of the aorta. The results suggested that clinically relevant discrepancies can particularly be expected when the aorta is small (diameter <3 cm). This could be confirmed by the present clinical study. Although the extent of pressure recovery in absolute terms was relatively small in the majority of patients and the resulting differences in these may not be of clinical relevance, overestimation of peak catheter gradients by Doppler of 20 mm Hg or more was found in seven patients with differences as great as 75 mm Hg for peak and 48 mm Hg for mean gradients. All of them had an aorta with less than 3 cm in diameter. The patient with the greatest discrepancy had a hypoplastic aorta with a diameter of only 1.7 cm.

Based on fluid mechanics theory, pressure recovery in relative terms depends on the ratio of orifice area and cross-sectional area of the aorta, as this ratio determines the extent of the dissipation of kinetic energy due to flow separation and vortex formation (1,2)(see eq. 1 and 2). However, in the clinical setting the size of the aorta should be the most important variable. Assuming an aorta greater than 3 cm in diameter, an aortic valve area still allowing the occurrence of relevant pressure recovery would have to be so large that a significant transvalvular pressure gradient is no longer realistic considering the possible range of cardiac output in a human being. Therefore, the size of the ascending aorta has to be in the lower normal range or smaller before clinically relevant pressure recovery can be expected. Pressure recovery in absolute terms of course increases with the orifice velocity according to their linear relationship (see equations 1 and 2[1,2]).

Correction of Doppler gradients for pressure recovery

We have also shown in vitro that pressure recovery in aortic stenosis can be predicted with Doppler echocardiography by calculating orifice velocity, aortic valve area and cross-sectional area of the aorta and using equation 2, as long as the stenotic jet is not highly eccentric (3). The present study suggests that this concept may indeed by useful in the clinical setting. While significant overestimation was found when noncorrected Doppler gradients were compared with catheter gradients, agreement was excellent when Doppler gradients were corrected for pressure recovery. Jet eccentricity, however, is difficult to assess in vivo, and the neglection of jet direction in the present study may have contributed to the scatter of the data. In addition, orifice morphology and blood viscosity that were not tested in the present study may affect pressure recovery.

It has been argued that the Doppler gradient that represents the actual maximal pressure drop across the stenosis is the more significant variable, since it characterizes the true tightness of the stenosis and should therefore not be corrected just to find better agreement with the gradient obtained by catheterization (12). However, from a physiologic point of view, it is the net pressure drop as obtained by distal pressure measurements including pressure recovery that reflects the hemodynamic significance of a stenosis, because this pressure drop determines the left ventricular pressure that is required to maintain a certain systemic arterial pressure.

Comparison to previous studies

In the past, several studies compared Doppler and catheter gradients in patients with aortic stenosis and found good agreement despite neglection of the phenomenon of pressure recovery (7–9). This may be explained by several reasons.

First, most studies indeed included some patients with marked overestimation of catheter gradients by Doppler, but this small minority did not significantly alter the overall results. Thus, these studies may simply not have included enough patients with small aortas to recognize the problem. Other investigators (11)reported slight but significant overestimation of catheter gradients by Doppler on average, with differences as great as 30 mm Hg. Again, information on the sizes of the patients’ aortas is not available. Nevertheless, the reported mean difference between Doppler and catheter mean gradients with 10 mm Hg is surprisingly close to the mean difference of 11 mm Hg found for the total patient group in the present study. Our study included a relatively high percentage of women. This may explain the larger number of patients with relatively small aortas and the mean diameter of 3 cm for the whole group, which may appear to be relatively small for adult patients with aortic stenosis who frequently have dilated ascending aortas. In addition, the present study includes a patient with a hypoplastic aorta and resulting highly significant Doppler overestimation of catheter gradients, which influences the results, particularly of the regression analysis, and makes the problem more evident. Thus, the better agreement between Doppler and catheter gradients in other reports (7–9)may mainly be due to differences in the patient populations and underrepresentation of patients with small aortas.

Second, overestimation of catheter gradients by Doppler may be more or less corrected by underestimation of the true maximal pressure gradient by Doppler due to other reasons, such as suboptimal alignment of Doppler beam and stenotic jet. Indeed, in the present study, 4 of 11 patients who had routine evaluation within one month before study examination were ultimately found to have gradients 12 to 34 mm Hg higher than previously reported. These differences reached or even exceeded the magnitude of pressure recovery in these patients and were primarily due to the fact that velocities were only measured from an apical approach. This highlights the importance of careful examination from all accessible windows. Finally, early studies may have been performed with less sensitive Doppler equipment, leading to some underestimation of true maximal gradients by Doppler.

Limitations of the study

In the present study, left ventricular and aortic pressures were not simultaneously measured in all patients. However, in those patients with simultaneously measured gradients, results did not significantly differ from those obtained by carefully performed computer-assisted pullback measurements. Also, Doppler and catheter measurements were not simultaneously obtained. However, invasive and noninvasive studies were performed within 24 h at stable conditions in all patients, and special care was taken to collect the data at comparable heart rates (all patients in sinus rhythm). Simultaneous measurements in the catheterization laboratory generally suffer from suboptimal conditions for such demanding Doppler examinations.

Furthermore, pressure recovery was not directly measured by invasive technique and usage of standard protocols did not make sure that distal pressure measurements were obtained at sites where pressure had recovered to its full extent. Theoretically, the distance required for full pressure recovery depends on the orifice size and aortic diameter (1,2). However, previous in vitro studies (3,5,6,12)have shown that most of pressure recovery occurs within several cm and that differences between wall measurements at 5 cm and central measurements at 10 to 20 cm downstream from the stenosis are small and clinically not relevant. This is not surprising since the distance for the occurrence of pressure recovery increases with the diameter of the aorta whereas a large size of the aorta precludes clinically significant pressure recovery. Furthermore, a clinical study (4)suggests that all measurable increase of pressure occurs within the ascending aorta. Thus, the measurement technique used in this study should reflect pressure recovery to a great extent. Finally, the good agreement between predicted pressure recovery and “observed pressure recovery” (i.e., the difference between Doppler and catheter gradient) supports that Doppler measured the highest gradient based on the lowest pressure in the vena contracta and that catheter measurements involved the maximally recovered distal pressure. In addition, we have previously shown in vitro that Doppler indeed measures the maximal gradient and that the performed catheter measurements allow the detection of pressure recovery accurate enough for clinical purposes (5,6). Finally, stenosis morphology, aortic morphology, and blood viscosity may affect pressure recovery but have not been studied. However, only two patients in the study had congenital aortic stenosis whereas the remainder had calcified stenoses where additional morphologic assessment is difficult. None of the patients happened to have circumscript aneurysmatic dilation of the aorta and all of the patients presented with a hematocrit within the normal range.

Clinical implications

The results of the present study confirm previous experimental work indicating that clinically relevant pressure recovery can occur in aortic stenosis and that it can cause significant discrepancies between Doppler and catheter gradients. The occurrence of a clinically relevant magnitude of pressure recovery, however, appears to require a size of the ascending aorta in the lower normal range or smaller. This may only be the case in a minority of adult patients with aortic stenosis, and explains why acceptable agreement between Doppler and catheter gradients can frequently be found despite neglection of pressure recovery. However, as demonstrated in this study, discrepancies between Doppler and catheter gradients can reach values as great as 75 mm Hg in individual patients. Assuming that the net pressure drop across a stenosis reflects its actual physiologic significance, this phenomenon could indeed lead to misjudgment of stenosis severity from Doppler data in some patients. Considering that a mean gradient ≥50 mm Hg in the presence of normal flow indicates hemodynamically severe stenosis, the severity of the disease would have been overestimated by Doppler in four patients in the present study by reporting severe instead of moderate aortic stenosis.

However, since the size of the aorta is the most important predictor of pressure recovery in aortic stenosis and can easily be measured by two-dimensional echocardiography, this should be used as an easily obtainable important clue as to whether this phenomenon requires consideration in a given patient. The results of the present study as well as those of previously reported in vitro work suggest that clinically relevant pressure recovery is highly unlikely when the diameter of the aorta is larger than 3 cm. Only in patients with an aorta smaller than that does pressure recovery deserve consideration. In this case, it appears feasible to predict the extent of pressure recovery and, therefore, the net pressure drop across the stenosis from the continuous-wave Doppler velocity of the stenotic jet, the aortic valve area as obtained with the continuity equation and the cross-sectional area of the ascending aorta. These results may help to further improve the accuracy and reliability of the assessment of aortic stenosis by Doppler ultrasound.