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European Journal of Heart Failure 2001 3(5):553-560; doi:10.1016/S1388-9842(01)00166-0
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© 2001 European Society of Cardiology

Feasibility and accuracy of transthoracic Doppler echocardiographic estimation of pulmonary capillary wedge pressure applying different methods

Gerhard Poelzla,*, Martin Gattermeierb, Horst Kratzerb, Eduard Zeindlhoferb and Peter Kuehnb

a Department of Internal Medicine, Division of Cardiology, University of Innsbruck Anichstr. 35, A-6020 Innsbruck, Austria
b 2nd Department of Internal Medicine KHd Barmh. Schwestern, Linz, Austria

* Corresponding author. Tel.: +43-512-504-4118; fax: +43-512-504-3379. E-mail address: gerhard.poelzl{at}uklibk.ac.at (G. Poelzl)


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 
Background: Pulmonary wedge pressure (PWP) is an established index of cardiac function and an essential component in the management of patients with congestive heart failure and in critically ill patients.

Aim: To evaluate feasibility and accuracy of non-invasive prediction of PWP by Doppler echocardiography in daily clinical practice.

Methods: Agreement was assessed between values predicted by Doppler vs. invasively measured PWP. Forty-five consecutive patients [mean (S.D.) age 62 (10) years] with CAD (44%), DCMP (40%) and without structural heart disease (16%) were studied (EF ≤ 40% in 58% of the patients). Doppler transmitral and pulmonary venous flow velocity profiles were recorded. For binary and quantitative prediction of PWP, four different methods and five different linear equations, suggested previously in the literature, were evaluated.

Results: Predictive values to identify elevated PWP were highest for pulmonary venous flow reversal exceeding the duration of forward mitral flow during atrial systole (PPV 1 and NPV 0.96). Likewise, agreement with measured PWP was highest for equations comprising both transmitral and pulmonary venous flow variables (relative mean difference 0.11, S.D. ± 4.01 mmHg for the most accurate equation). Feasibility was slightly, but not statistically, lower when pulmonary venous flow was considered vs. transmitral flow parameters alone for binary prediction (87 vs. 93%) as well as for quantitative assessment (82 vs. 93%).

Conclusion: Semiquantitative prediction of elevated PWP by Doppler echocardiography is feasible as well as accurate in daily clinical practice. However, accuracy of numeric estimates is limited. Hence, invasive measurement of PWP is still necessary in certain clinical settings.

Key Words: Left ventricular filling pressure • Doppler echocardiography

Received October 23, 2000; Revised February 20, 2001; Accepted April 25, 2001


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 
Left ventricular (LV) filling pressure and its widely used approximation by pulmonary wedge pressure (PWP) is a crucial index of cardiac function [1]. The knowledge of LV filling pressures is frequently needed in critically ill patients for diagnostic and therapeutic purposes [2]. In patients with chronic heart failure, a high pulmonary wedge pressure is associated with low exercise tolerance, severe symptoms and poor prognosis [3–5]. Hemodynamically tailored therapy yields an improved quality of life and increased exercise performance [6,7]. Direct hemodynamic evaluation, however, is restricted to invasive and hence risky and costly procedures such as Swan–Ganz catheterization [8].

In the past decade, various methods have been proposed to estimate LV filling pressure non-invasively by transthoracic Doppler echocardiography. Several Doppler parameters (Table 1) predict elevated LV filling pressure with reasonable sensitivity and specificity [9–11]. Accordingly, good correlation to invasive measurements have been found for the estimates derived from different linear equations (Table 2) comprising various Doppler parameters of transmitral flow with or without additional variables of pulmonary venous flow recordings [12–15].


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  		Table 1 Suggested Doppler flow variables for binary prediction of elevated LV filling pressure

 


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  		Table 2 Suggested linear equations for the prediction of left ventricular filling pressure by Doppler echocardiography. In the text different equations are referred to as equations 1–5

 
However, to introduce a non-invasive estimation of a crucial hemodynamic parameter as a substitute for an invasive measurement into daily clinical practice, the following requirements need to be met: (1) feasibility in most of the patients; and (2) accuracy in individual patients.

Hence, the aim of this investigation was to evaluate the proposed methods in the ‘real world’ of a tertiary care center for cardiology with associated intensive care unit (ICU).


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 
2.1. Study patients
The patient population consisted of 45 consecutive patients (18 women, 27 men, mean age (S.D.) 62 (10) years, range 28–75) in hemodynamically stable conditions referred for diagnostic heart catheterization and coronary angiography for suspected coronary artery disease (34 patients) or in hemodynamically unstable conditions admitted to the ICU (11 patients, six of whom were on mechanical ventilation).

Exclusion criteria were arrythmias, in particular atrial fibrillation, cardiac pacing, prolonged PR-interval, mitral stenosis and more than mild mitral or aortic regurgitation on Doppler echocardiography.

2.2. Echocardiography
Standard transthoracic M-Mode, two-dimensional and Doppler echocardiographic studies were performed with a commercially available Doppler echocardiograph (Vingmed CFM 750/800, Norway) with a combined 3.25 MHz imaging/2.5-MHz Doppler transducer.

Mitral and aortic regurgitation were detected by color Doppler echocardiography and graded according to standard criteria [16].

Mitral flow and pulmonary venous flow velocities were obtained by pulsed Doppler technique from a two-dimensional apical four-chamber view. Continuous-wave Doppler recording was performed for determination of isovolumic relaxation time (IVRT) as previously described [14].

Recordings were obtained during quiet respiration at a sweep of 50 mm/s, the high pass filter was set as high as possible. All examinations were recorded on videocassette recorder (Panasonic AG-7350, Japan) for later playback and analysis. Calculations were made by tracing modal velocities and use of the analytic software in the ultrasound machine. The average value of at least three consecutive beats was used for quantitative analysis.

2.3. Mitral flow analysis
Mitral flow velocities were obtained with the sample volume positioned between the tips of the mitral leaflets, where maximal flow velocity is recorded [13].

The following parameters were measured: peak early (E) and atrial (A) flow velocity (cm/s); E/A ratio; A wave duration (dA or MA) (ms); DT or DecT (measured as the interval from peak early velocity to the zero intercept of the extrapolated deceleration slope) of E and A; AFF, atrial filling fraction (calculated as the ratio of the integral of the A wave to the total integral of the mitral flow velocity); and MAR (measured as the interval from the end of the A wave to the R wave on the ECG) (ms). IVRT (ms) was measured as the interval from the end of aortic flow velocity to the onset of mitral flow. DR (m/s2) was calculated by dividing E (m/s) by DT of E (s).

2.4. Pulmonary venous flow analysis
Pulmonary venous flow velocities were obtained with a sample volume placed 0.5–1 cm into the upper right pulmonary vein [11].

The following pulmonary venous flow variables were measured: peak forward flow velocities during systole (S) and diastole (D) (cm/s); systolic fraction of pulmonary venous flow (SF) defined as S divided by the sum of S and D; pulmonary venous A wave duration (dZ or PA) (ms); ratio of mitral A wave duration to pulmonary A wave duration (MA/PA); difference in duration between dZ and dA (ms).

If velocity signals of atrial flow reversal were not of sufficient quality to provide direct measurement of dZ (PA), this parameter was obtained by measuring the interval between the end of the diastolic forward flow and the onset of systolic forward flow or by comparing the time intervals between the end of the flow signals and the R wave on the ECG [11].

2.5. Calculation of PWP
For binary prediction of elevated LV filling pressure defined as PWP>15, >18, ≥20 mmHg, respectively, different Doppler flow variables were considered as published previously by various authors (Table 1) [9–11].

Quantitative assessment of PWP was based on five different linear equations comprising various Doppler parameters of transmitral flow with or without additional variables of pulmonary venous flow recordings as suggested previously in the literature (Table 2) [12–15].

2.6. Cardiac catheterization
Right heart catheterization was performed through the femoral or the sub-clavian approach with a ballon-tipped pulmonary artery catheter (Swan-Ganz, Baxter Healthcare Corp., USA) connected to a strain-gauge transducer (pvb medizintechnik gmbh and co kg, Germany). The zero reference point was taken at mid-chest. Hemodynamic measurements were obtained before any injection of contrast medium. After a 5-min rest for stabilization pulmonary wedge pressure was obtained at end-expiration.


   3. Statistical analysis
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 
If TP, TN, FP and FN denote true positives, true negatives, false positives, and false negatives, respectively, then sensitivity, specificity, positive predictive value and negative predictive value were computed as TP/(TP+FN), TN/(TN+FP), TP/(TP+FP), and TN/(TN+FN), respectively. Differences between the estimates of equations 1 to 5 and the invasively measured PWP's were assessed using the Bland and Altman method [22]. Linear regression was used to assess dependency of estimation error on true PWP values. McNemar's test with Bonferroni-Holm correction for multiple testing was used to compare feasibility of the applied methods and equations, respectively. P-values <0.05 were considered as indicating statistical significance.


   4. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 
The underlying heart disease was coronary artery disease (CAD) in 20 (44%) and dilated cardiomyopathy (DCMP) in 18 patients (40%). No structural heart disease was found in seven patients (16%). LV function was impaired (EF≤40%) in 26 patients (58%).

Doppler echocardiographic evaluation was performed either simultaneously in hemodynamically unstable patients at the ICU or within 60 min before invasive measurement in hemodynamically stable patients. Differences in heart rate (80 vs. 81 bpm) and systolic blood pressure (136 vs. 132 mmHg) between Doppler studies and invasive measurements were not statistically significant. Tracings of sufficient quality of the transmitral and pulmonary venous Doppler flow were obtained in 93 and 89%, respectively.

4.1. Binary analysis
The ability of four different methods to predict elevated PWP in terms of sensitivity, specificity, positive and negative predictive value and feasibility are shown in Table 3. Highest sensitivity and specificity to predict elevated mean pulmonary wedge pressure were obtained for pulmonary venous flow reversal exceeding the duration of forward mitral flow during atrial systole (PA>MA). The use of transmitral flow parameters only (E/A>2, DecTE<120 ms, DecTA≤60 ms) provided less sensitivity and comparable specificity although feasibility was higher. Accordingly, positive predictive value (PPV) and negative predictive value (NPV) were highest for PA>MA.


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  		Table 3 Sensitivity, specificity and predictive values for binary prediction of elevated left filling pressures using different Doppler flow variables

 
Similar results were seen when analyzing sub-groups of patients, PA>MA predicted pulmonary wedge pressure >15 mmHg with a PPV and a NPV of 1 or very close to 1 (results not shown) irrespective of: (1) whether left ventricular ejection fraction was low (EF≤40%) (Table 3) or high (EF>40%); (2) age was below or above 60 years; (3) the etiology of the underlying heart disease (CAD, DCMP or none); and (4) the fact that patients were mechanically ventilated (four of six patients were on mechanical ventilation with continuous positive airway pressure not exceeding 5 mbar).

4.2. Quantitative analysis
The mean relative difference between estimated and measured PWP was close to 0 for Eq. 4 and within an acceptable range for Eqs. (2), (3) and (5) (–0.6, –1.5 and 1.1, respectively) indicating the absence of relevant systemic error (Fig. 1). However, the standard deviations of differences were less when PWP was estimated by Eqs. (4) and (5) (Fig. 1). Eq. (1) was the least accurate (Fig. 1).


Figure 1
Figure 1
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  		Fig. 1 (a–e) Bland–Altman plots of differences (y-axis) between estimated and measured pulmonary wedge pressure (delta-PWP) vs. their mean values (x-axis). Eqs. (1)–(5) were used to estimate PWP. The relative mean difference between estimated and measured PWP was close to zero for Eq. (4) with minor deviations for Eqs. (2), (3) and (5). Standard deviations (S.D.) were in fact smallest for Eqs. (4) and (5), but still sufficiently large to limit the accuracy of numeric estimates to reliably predicted PWP in an individual patient. Regression analysis (results not shown) revealed that the estimation errors of Eqs. (2)–(5) were negatively correlated with true PWP values (all P<0.05) indicating overestimation and underestimation of low and high PWP values, respectively. Eq. (1) tended to overestimate irrespective of the given PWP.

 
A negative correlation of estimation errors of Eqs. (2)–(5) with the true PWP values was found by regression analysis indicating overestimation and underestimation of low and high PWP values, respectively.

Feasibility was highest, although statistically not significant, for Eq. (1) and (3) (93%) vs. 91% for Eq. (2) and 82% for Eqs. (4) and (5).


   5. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 
The main results of our study were: first, that feasibility of estimation of PWP by transthoracic Doppler echocardiography in daily practice is as high as 93%; second, that PPV and NPV for binary prediction of elevated LV filling pressure were 1 and 0.96, respectively; and third, that accuracy to predict PWP was highest when Doppler echocardiographic variables of mitral and pulmonary venous flow were considered.

Previous studies found a strong correlation between invasively measured LV filling pressures with numeric estimates derived from linear equations comprising Doppler echocardiographic variables from mitral flow with or without variables from pulmonary venous flow [12–15]. Similarly, several Doppler flow variables have been shown to differentiate between patients with normal and elevated left ventricular filling pressures with high sensitivity and specificity [9–11]. However, the translation of these study findings into daily clinical practice is limited by several factors:

  1. Some of the studies encompass relatively selected patient groups and thus prevent generalization of the findings.
  2. For clinical purpose, predictive values for binary tests as well as agreements for numeric tests are of greater value than correlation, which is provided by some studies.
  3. Different invasive measurements (left ventricular end-diastolic filling pressure, pulmonary wedge pressure) were used to estimate LV filling pressures.

Hence, the aim of this study was to evaluate how far these study findings meet the demands of daily clinical practice.

The difference in duration between pulmonary venous flow reversal and forward mitral flow during atrial systole (PA>MA) was found to be the best predictor of elevated left ventricular filling pressure irrespective of the underlying heart disease, irrespective of the age of the patients and irrespective of the LV function (Table 3). This method was feasible in 87% of all patients.

Mitral Doppler flow variables (E/A>2, DecTA≤60 ms) provided high PPV to predict elevated PWP in all patient groups, however, at the expense of lower NPV. A strong correlation between PWP and deceleration time of early diastolic mitral flow (DecTE) in post-infarction patients with left ventricular dysfunction was found by Gianuzzi et al. [9]. In our study, NPV was high and PPV was low for DecTE<120 ms. This was mainly due to the high cutoff point of 20 mmHg (Table 3).

In a previous study, correlation of early diastolic Doppler indices with LV filling pressures was high in patients with systolic dysfunction, but weak in patients with preserved systolic function [23]. In the present study, however, when Doppler indices were applied to predict elevated PWP in a binary manner, no differences in predictive accuracies were seen in both patients with and without systolic dysfunction (Table 3).

Although binary distinction between elevated and normal PWP may be helpful in various clinical settings, quantitative assessment is often necessary for guiding therapeutic interventions [7].

In our study, numeric agreement with invasive measurements was highest for Eqs. (4) and (5), which combine Doppler echocardiographic variables from mitral and pulmonary venous flow (Fig. 1). However, standard deviations of differences were higher in our hands than in the study of Pozolli et al. when Eqs. (4) and (5) were suggested for the first time [15]. This might be due to the heterogeneous group of patients investigated in our study.

Regression analysis revealed a trend to underestimation and overestimation in patients with very low or very high PWP's, respectively.

Feasibility was slightly, but not statistically, significantly lower for Eqs. (4) and (5) vs. equations considering mitral flow variables only (82 vs. 93%). Pulmonary venous flow was not available mostly because in very large hearts the sample volume of pulsed Doppler could not be positioned into the pulmonary vein. Notably, feasibility did not drop substantially in patients admitted to the ICU (73%) and was as high as 83% in the subgroup of ventilated patients. Recently, it has been suggested that feasibility can be even further improved by applying contrast agents [24]. Mitral Doppler flow could not be depicted adequately in patients with tachycardia resulting in merging of E and A wave.

Thus, corresponding to what has already been suggested by several authors, it was confirmed in our study that binary prediction of elevated LV filling pressures as well as quantitative assessment by Doppler echocardiography was superior when combining mitral and pulmonary venous flow variables [17–20].

In summary, transthoracic Doppler echocardiography provides a convenient bedside test to distinguish between patients in whom pre-load reduction or volume challenge is indicated in approximately 90% of patients. Because of its ease, the suggested methods may serve as an eyeball index, which are available within a few min.1

However, when applying quantitative assessment of LV filling pressure by Doppler echocardiography into clinical practice it has to be taken into account that standard deviations from the relative mean differences between estimated and measured PWP were sufficiently large for all equations to limit the accuracy of numeric estimates to reliably predict PWP in an individual patient. This seems especially true in patients without structural heart disease and in patients with very low or very high filling pressures. Hence, caution in interpretation of estimates is advisable. We therefore suggest to always verify the Doppler estimates by applying one, preferably several binary Doppler methods, which can already provide a rough approximation of the PWP. Additionally, echocardiographic findings (e.g. LV function and dimension) as well as physical signs should be considered.


   6. Study limitations
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
7. Conclusion
 Notes
 Acknowledgments
 References
 
The main limitation in this study was the exclusion of patients with arrhythmias, in particular atrial fibrillation and patients with cardiac pacing, prolonged PR-interval, mitral stenosis and more than mild mitral or aortic regurgitation, who, as a group, represent a relevant part of the population in daily clinical practice.

Although there is a well-established close correlation between left ventricular end-diastolic filling pressure (LVEDP) and PWP, the former may exceed the latter in some patients such as those with an acute myocardial infarction [21]. Furthermore, E/A>2, PA>MA and Eq. (2) were validated for predicting LVEDP only. In our study, PWP and LVEDP were set equal for allowing comparison of the results. This seems to be justified since for clinical decision making PWP is used rather than LVEDP.

PWP was measured with a fluid-filled catheter, whose technical limitations are well known. However, this method is sufficiently reliable and routinely used in clinical practice.

Doppler estimates and invasive measurements were not obtained simultaneously in 34 patients (76%). A relevant change in filling pressure appears unlikely, though, because these patients were in hemodynamically stable conditions, the time intervals between the tests did not exceed 1 h, there was no significant difference seen in heart rate and blood pressure between the Doppler studies and the invasive measurements and no drugs were given in the time between the studies.


   7. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
Notes
 Acknowledgments
 References
 
Our results provide evidence that binary prediction of elevated LV filling pressure by Doppler echocardiography in daily clinical practice is feasible as well as accurate. However, accuracy of quantitative assessment of PWP by Doppler echocardiography cannot be predicted consistently in individual patients.

In our experience, Doppler echocardiographic assessment of elevated LV filling pressure is of particular value in the management of patients with heart failure, and, because of its ready accessibility, in the initial evaluation of hemodynamically unstable patients.

Right heart catheterization may be reserved for patients in whom frequent and precise measurement of PWP is pivotal, patients with poor Doppler tracings and patients who meet the exclusion criteria used in this study.


   Acknowledgments
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
References
 
We are indebted to Prof. H. Baumgartner, M.D., General Hospital Vienna, for his thoughtful review of the manuscript.


   Notes
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
Acknowledgments
 References
 
1 For assessing PA>MA, the termination of both A wave flows can be referenced to the QRS-complex as a rapid means of determining which flow has the longer duration because the beginning of mitral and pulmonary venous A waves is simultaneous [17]. Back


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 6. Study limitations
 7. Conclusion
 Notes
 Acknowledgments
 References
 

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