This study evaluated the utility of echocardiography for the estimation of pulmonary hemodynamics and CO in a population of patients referred for right-heart catheterization at a single PH center. Both tests were completed sequentially and within a very short timeframe (1 hour). Despite these optimized conditions, echocardiographic estimates for right atrial and pulmonary artery pressures differed significantly from those determined by invasive measurements, as assessed by Bland-Altman analysis, with a tendency to both overestimate and underestimate the pulmonary artery systolic pressure. Underestimations were larger in magnitude and more often significantly misclassified the severity of PH. Finally, measurements of CO by DE, which has been validated in other patient populations, appeared least useful.
Clinical interest in using DE to estimate right ventricular pressure arose after Berger and colleagues and Currie and colleagues demonstrated good correlation between echocardiographic estimates and directly measured pressures (6
). However, establishing good correlation does not imply that one test is an accurate substitute for another. More recent studies have focused on the value of echocardiography in assessing RV function by various techniques, including measurement of the tricuspid annular plane systolic excursion (TAPSE), two-dimensional strain, tissue Doppler echocardiography, or the speckle tracking method (3
). However, RV systolic pressure (RVSP) remains the most commonly emphasized echo-derived parameter in routine clinical practice, particularly as the diagnosis of PH often hinges upon its initial recognition by Doppler echocardiography. Also, direct comparisons of echocardiographic estimates (e.g., RVSP) and hemodynamic values obtained by right-heart catheterization, with the two procedures being performed within an acceptable time frame, have been relatively lacking in PH studies.
Bland and Altman developed statistical methods to better assess the equivalence or accuracy of one test compared with another (14
), which we used for the present study. The Bland-Altman method is arguably a more optimal way to compare two numerical tests. Although conclusions from the present study (related to the accuracy of DE) are at odds with those reached by Berger and colleagues and Currie and colleagues, they are in agreement with studies by Arcasoy and colleagues and Fisher and colleagues (8
). The former study assessed the utility of DE in patients with advanced lung disease who had been referred for lung transplantation. Although DE values correlated with hemodynamic measurements (the two studies were performed within 72 hours of each other), DE was found to be frequently inaccurate and to overestimate the degree of PH. The latter study related to patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial (NETT), using a similar Bland-Altman analysis in these patients with end-stage chronic obstructive pulmonary disease (COPD); the authors concluded that DE estimates of pulmonary artery pressures correlated very poorly with hemodynamic measurements obtained by cardiac catheterization. In addition, the DE test characteristics of sensitivity and specificity were also poor. The temporal relationship between the DE and hemodynamic measurements in that study was not defined. In another comparison of DE and right-heart catheterization limited to a population of patients with scleroderma (19
), and in which the mean interval between the two techniques was an average of 1.8 months, Denton and colleagues found a good correlation (R
= 0.83, P
< 0.001), however, with large discrepancies in pulmonary artery systolic pressures (PASP), of over 20 mm Hg in approximately 25% of patients, between the two techniques, particularly with increasing PASP. Nevertheless, the authors felt that DE was a useful technique to detect PH in this particular population. In a more recent study of 42 patients with various forms of PH in whom DE was performed simultaneously (in 22 patients) or nonsimultaneously (60 patients, some with repeated measurements) with cardiac catheterization (with the two procedures separated by up to 48 hours), Selimovic and colleagues found good correlations and small absolute differences for PASP and CO between the two approaches (20
). However, large discrepancies in individual values for CO and transpulmonary gradient were found.
The present study extends the findings of these previous studies to a more assorted, and clinically relevant, population of patients with pulmonary arterial hypertension (PAH; which constituted 68% of our patient sample) as well as other causes of PH. Moreover, our study addresses important limitations of some of these previous studies in being prospective rather than retrospective and limiting the interval between invasive and noninvasive measurements to 1 hour, thus obviating as much as possible potential daily variations in hemodynamic measurements. Importantly, unlike the study by Selimovic and colleagues, we excluded repeated measurements in the same patients, which has the potential to bias results (e.g., if an individual had particularly good or poor echocardiographic windows) and is not appropriate when performing a Bland-Altman analysis. In the present study, demonstrates that PASP obtained by DE was frequently underestimated, often to a significant extent, particularly when quality of the Doppler envelope was fair or poor. This is expected because the accuracy of the Doppler method is contingent upon obtaining the correct peak velocity from which the peak pressure can be estimated. Likewise, our data show that a lesser degree of TR is more common in patients with underestimated pressure by DE, which stands to reason. This data does not account for the six (excluded) subjects with no appreciable TR, four of whom had PH by right-heart catheterization. Thus, a complete or relative lack of TR, although typically associated with a more compensated right ventricle, should not be interpreted as “reassuring” for ruling out the presence of PH. Of note, 12 of 15 patients in whom PA pressure was underestimated by DE had evidence of RV enlargement and/or dysfunction on their DE exam, supporting the notion that the clinician should integrate evidence of RV size and function, along with pressure estimates in the overall DE interpretation.
The PASP was overestimated even when the envelope quality was adequate, with the absolute degree of pressure overestimation greatest at higher pressures. Interestingly, when we evaluated the validity of echo-estimated RAP, we found a wide spread between values obtained by DE and right-heart catheterization, particularly when RAP pressures were deemed elevated by DE (). In fact, an inaccurate RAP estimate accounted for half of the cases of noninvasive pressure overestimation. Therefore, these results indicate that the size of the IVC, and its variation with respiration routinely used to estimate RAP, may not be as useful as commonly believed in patients with chronic pulmonary hypertension.
Our data also demonstrate that from a diagnostic or clinical perspective, pressure underestimation was more likely to lead to gross misclassification of the degree of PH in the individual patient; 47% of subjects whose pressure was underestimated by Doppler were misclassified by two or more diagnostic categories (e.g., severe PH by invasive measurement, estimated to be mild PH by DE exam). In contrast, only 13% of subjects with pressure overestimation by Doppler had gross misclassification of their PH severity by DE exam. Therefore, the pressure underestimations were not only greater in magnitude but also more clinically misleading. These data serve to underscore the importance of pursuing definitive PA pressure assessment by right-heart catheterization in the patient with suspected PH if there is uncertainty about the DE estimated value for whatever reason, may it be a suboptimally visualized Doppler signal across the tricuspid valve or evidence of RV dysfunction.
In addition, our study is the first to evaluate the accuracy of echocardiographically estimated CO in a large group of patients with PH. The wide 95% limits of agreement between the thermodilution CO and the noninvasive estimate suggests that echocardiography has limited utility in this patient population in assessing CO, a finding that was suggested in the smaller study by Selimovic and colleagues (20
). However, the discrepancies between the DE assessment and the hemodynamic values were smaller when CO was low (). Therefore, it is unlikely that changes involving the left ventricle or diastolic ventricular interaction (more common in severe pulmonary hypertension where CO is expected to be low) would significantly affect the accuracy of DE assessment. Some of the noted discrepancy between the two measurements may be due to inherent and clinically “acceptable” variability in the invasive CO estimation by thermodilution, recognizing that an average of three values is taken, allowing up to 10% variation between each measure. Although some reports have shown consistent CO underestimation by the thermodilution method in subjects with significant TR, others have demonstrated that in patients with severe PH, even in the presence of significant TR, the thermodilution has acceptable agreement with the Fick method (21
). In addition, in animal models, the creation of acute tricuspid regurgitation has been shown not to affect thermodilution cardiac output measurements (22
). In our study, there did not appear to be a serial underestimation of CO in the subgroup of patients with moderate or greater TR (mean bias −0.04 L/min), making TR-related CO underestimation by thermodilution an unlikely culprit for the discrepancies seen between CO estimates by thermodilution and Doppler here. There was a high, but imperfect correlation between heart rate at the time of the catheterization and the DE (r
= 0.88), making heart-rate variability a potential but likely minor contributor to the CO differences between the two methods. Another known limitation, and thus source of variability, inherent to this Doppler method of CO estimation is that the diameter of the LVOT must be squared, thus, error in LVOT diameter estimation is subject to amplification (23
). This latter issue can be circumvented by simply using the VTI as a surrogate for stroke volume and thus cardiac index. In our dataset, a VTIRVOT
less than 12 was a relatively accurate predictor of a cardiac index 2.2 or less, suggesting that easily derived Doppler echocardiographic data can still be used to provide insight into cardiac output in PH patients. Similarly, we recently showed that a TAPSE less than 1.8 was an accurate predictor of a stroke volume index ≤28 ml/m2
; thus, even if we cannot obtain precise CO estimations by Doppler, a more integrated use of easily obtained Doppler and 2D echocardiographic measures can still provide useful information in identifying patients with a low cardiac index (3
A potential limitation of this study is that the two measurement methods were not performed simultaneously, which has been done previously only in a small subset of patients (20
). However, we felt that performing DE in the catheterization laboratory in a large group of patients studied prospectively would have interfered with adequate hemodynamic measurements and rendered the study technically difficult. Pulmonary pressures in patients with PAH are known to fluctuate significantly over the course of several hours as demonstrated by Rich and colleagues (24
). However, the degree of variation noted in our study is far greater than would be expected in such a short time frame without any interventions or change in position or activity (patients were left idle in the supine position during the time, equal to or less than an hour, separating the two procedures). Additional sources of variability are also inherent to obtaining accurate hemodynamic pressure recordings, and thus, for every patient, appropriate transducer position relative to the heart, zero-referencing, and obtaining pressures at end-expiration, were part of standard procedure to minimize these potential issues. Because the study assessed only one time-point, it does not address the validity of following trends in serial measurements. However, based on significant differences between these two methods at one time-point, addressing serial comparative measurements appears futile.
In conclusion, we believe that DE remains an invaluable screening tool for the evaluation and further management of PH. However, our study underlines the significant limitations of DE when used to evaluate right-sided cardiac pressures and CO in patients with PH. DE does not always accurately reflect pulmonary artery and right atrial pressures and can significantly under- or overestimate these values in individual patients. Particular caution should be exercised in assessing PA pressure by DE when the TR jet quality is low, as serious pressure underestimations can occur, leading to missed or delayed diagnosis of a disease with high morbidity and mortality. DE has also been shown to provide an estimate of PVR, measured as the ratio of the tricuspid regurgitant velocity (TRV) to the VTI of the right ventricular outflow tract (RVOT). TRV/VTIRVOT
has been shown to predict mortality and adverse cardiovascular events in patients with stable coronary artery disease (25
). However, because the relation of TRV/VTIRVOT
to PVR has been established in a population with an average PVR of 2 mm Hg/L/min, its application in patients with very high PVR values (i.e., pulmonary vascular disease) remains to be determined. In addition, acceleration time of the pulsed wave Doppler velocity envelope in the RV outflow tract correlates reasonably well with mean PA pressure and, unlike estimates based on tricuspid regurgitation velocity, is available in virtually all patients (26
). Regression equations have been proposed to estimate mean pulmonary artery pressure based on echocardiographic findings (27
), including formulas using pulmonary artery acceleration time (PAAT), which are somewhat heart rate–dependent but correlate well with mean pulmonary artery pressure in patients with heart rates between 60 and 100 per minute (29
In summary, DE remains an indispensable screening tool for the assessment of PH; however, clinicians should not be overly reliant on Doppler pressure estimates alone in the initial approach to the patients with suspected PH. Moreover, it cannot be overemphasized that DE does not replace cardiac catheterization for definitive hemodynamic assessment of known or suspected PH. Furthermore, we feel that DE may not be very useful when used serially in assessing changes in pulmonary artery pressure in response to therapy (although this was not specifically addressed in our study), due to significant individual over and underestimation of pressures, which underscores the importance of taking other echo-derived metrics (i.e., measures of RV size and function) into consideration as well. The validity of specific DE measurements or combination of measurements for that purpose will only be answered in carefully designed prospective studies. Finally, this study suggests that DE may be of limited value for the assessment of CO.