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European Journal of Echocardiography 2003 4(3):162-168; doi:10.1016/S1525-2167(02)00160-9
© 2003 by European Society of Cardiology
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Copyright © 2003, The European Society of Cardiology

Non-invasive estimation of left ventricular end-diastolic pressure by pulmonary venous flow deceleration time

A Olariu, E Wellnhofer*, M Gräfe and E Fleck

Klinik für Innere Medizin/Kardiologie Deutsches Herzzentrum Berlin, Berlin, Germany

Received 9 January 2002; accepted after revision 9 October 2002.

* Address correspondence to: Ernst Wellnhofer, Klinik für Innere Medizin/Kardiologie, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel/Fax: +49 30 4593 2463. ewellnhofer{at}t-online.de


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Aims: The scope of this study was to assess the potential value of pulmonary venous flow diastolic deceleration time to predict end-diastolic pressure and stratify patients with regard to elevation of left ventricular end-diastolic pressures.

Methods and Results: In 174 consecutive patients, pulmonary venous flow diastolic deceleration time was determined and compared with left ventricular end-diastolic pressures measured invasively. The sample was randomly divided into two subgroups of equal size for modelling of prediction and independent testing of the model. Predicted left ventricular end-diastolic pressures calculated from pulmonary venous flow diastolic deceleration time (left ventricular end-diastolic pressures = –10.87 + 5261/pulmonary venous flow diastolic deceleration time) agreed well with measured left ventricular end-diastolic pressures (mean difference: -1.3 ± 3.4 mmHg). The correlation of left ventricular end-diastolic pressures with pulmonary venous flow diastolic deceleration time is fair (r=0.73989). A value of pulmonary venous flow diastolic deceleration time <220 ms is suggestive of elevated left ventricular end-diastolic pressures and should be monitored. A value of pulmonary venous flow diastolic deceleration time <190 ms predicts elevated left ventricular end-diastolic pressures. A value of pulmonary venous flow diastolic deceleration time <165 ms predicts severely elevated left ventricular end-diastolic pressures. With 190 ms as a cut-off value for elevated and 165 ms for severely elevated left ventricular end-diastolic pressures, cross-table analysis classifies all patients with normal left ventricular end-diastolic pressures correctly. No patient with severe elevation (<18 mmHg) of left ventricular end-diastolic pressures is classified as normal ({chi}2=102, P<0.0001).

Conclusion: Pulmonary venous flow diastolic deceleration time is an appropriate non-invasive measurement to stratify patients with respect to elevation of left ventricular end-diastolic pressures.

Keywords: AR the reversal of flow from the left atrium to the pulmonary veins during atrial contraction; vAR, dAR the velocity and duration of AR; E, A waves waves of the diastolic transmitral flow; E-dt deceleration time of the E wave; dA the duration of the A wave; IVRT isovolumic relaxation time


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
 References
 
Non-invasive estimation of the end-diastolic pressure, an important parameter in cardiac diagnostics, monitoring and therapy, is desirable. Several studies with different non-invasive parameters were previously performed to evaluate pulmonary wedge pressure (a substitute of left ventricular end-diastolic pressures) or left ventricular end-diastolic pressures[1–10]. None of these approaches has hitherto been established in clinical practice. Pulmonary venous flow diastolic deceleration time, which may be measured using a transthoracic approach even in arrhythmia, e.g. atrial fibrillation[11] has been found to correlate better with atrial pressure than mitral flow parameters[12] and was successfully used to estimate the pulmonary wedge pressure in several studies[10,11]. The subsequent study assesses the value of pulmonary venous flow diastolic deceleration time to predict end-diastolic pressure and stratify patients with regard to elevation of left ventricular end-diastolic pressures.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 References
 
One hundred and seventy-four consecutive patients (144 males, 30 females, mean age 43 years, range 26–94 years, 134 with coronary artery disease, 22 with dilatative cardiomyopathy, 18 with other diseases) presenting at the German Heart Institute Berlin between 25 June 2001 and 25 August 2001 for catheterization based on an independent indication not related to the study were investigated. Exclusion criteria were atrial fibrillation, mitral stenosis or prosthetic valve in mitral position, atrial septal defect, and inadequacy of transthoracic Doppler assessment (eight patients). Forty-seven patients had impaired ejection fraction (<45%). Twelve patients suffered from moderate to severe mitral regurgitation.

Informed consent was obtained from all patients. The study was performed in accordance with the Declaration of Helsinki.

Echocardiographic examination
The transthoracic echocardiographic examination was performed with the patients in left lateral position with an ATL HDI-5000 device and a 3.25 MHz transducer, and using second harmonic imaging.

Pulmonary venous flow diastolic deceleration time was determined from the apical four-chamber view. The pulsed wave sample volume (depth 0.5–1 cm) was positioned in the right upper pulmonary vein. Additional parameters determined in this position were velocity (vAR) and duration of reversal of flow from the left atrium to the pulmonary veins during the atrial contraction (dAR) (Fig. 1).


Figure 1
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  		Figure 1 Pulmonary venous flow measurements. The systolic part of pulmonary venous flow is marked ‘S’, the diastolic phase ‘D’ and atrial reversal ‘AR’. Deceleration time was determined as the time from the peak of the D-wave to the time of intersection of the deceleration slope with the baseline.

 
For the measurement of the transmitral diastolic flow parameters, the pulsed wave sample volume was located at the tips of the mitral leaflets in the apical four-chamber view. The peak velocity of E and A waves, the duration of the A wave (d-A) and the deceleration time of the E wave (E-dt) were measured (Fig. 2). The isovolumetric relaxation time was assessed by positioning the pulsed wave sample volume in the LVOT near the mitral leaflets in the three-chamber view, thus obtaining a simultaneous recording of mitral diastolic flow and antegrade flow into the aorta (Fig. 3).


Figure 2
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  		Figure 2 Transmitral diastolic flow measurements. The early diastolic filling wave is marked ‘E’ and the late diastolic filling wave ‘A’.

 


Figure 3
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  		Figure 3 Isovolumic relaxation time. The isovolumic relaxation time (IVRT) was measured as the time interval between the end of the artic flow and the start of the early diastolic flow.

 
All measurements were done in end expiration and repeated until successive measurements were nearly identical but at least three times. All examinations were performed immediately before the invasive pressure measurements.

Invasive examination
Informed consent was given by all patients prior to examination. Cardiac catheterization was performed according to standard clinical practice from a transfemoral approach. Pressure measurements were performed with a liquid-filled system (resonant frequency 12–15 Hz, damping coefficient ~0.2). Pressures were recorded together with an ECG by a Hellige® Midas monitoring system and printed on chart. The end-diastolic pressure was determined in the diastolic pressure tracing at the start of the R-wave in the ECG (average of 7–10 beats).

Statistical analysis
Data are presented as mean and standard deviation (SD). Correlation analysis was performed in all 174 patients (product moment or Spearman's correlation) to evaluate trends. The sample was subdivided into one group to establish the prediction by empirical data fitting and a second independent group to test the prediction. The patients were allotted at random to both equally large (n=87) groups. Left ventricular end-diastolic pressures were classified as normal (≤12 mmHg), slightly elevated or borderline (>12 and <18 mmHg) and severely elevated (≥18 mmHg). A cross-table analysis with {chi}2-test was performed in the test sample between the classification based on measured left ventricular end-diastolic pressure values and the classification based on the cut-off values for pulmonary venous flow diastolic deceleration time established in the fitting sample. A discriminant analysis was performed. Discriminant function, values of the discriminant function at the group centroids and the Mahalonobis distance, a measure the power of the discrimination, are presented.

Intra-observer variability of pulmonary venous flow diastolic deceleration time was assessed by mean square error (MSE) and variance coefficient of four serial measurements in 11 patients (mean difference, 7 ms; msE, 66 ms2; variance coefficient, 2.5%). The inter-observer variability was evaluated in 10 patients by two different blinded investigators (mean difference, 3 ± 6 ms; msE, 66 ms2; variance coefficient, 2.5%).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusion
 References
 
Pulmonary venous flow diastolic deceleration time was the only parameter that demonstrated a fair correlation with left ventricular end-diastolic pressures (r=–0.63959 linear model, r=–0.79974 non-linear model). This correlation was better in patients with impaired ejection fraction or severe mitral regurgitation (r=–0.85). IVRT and dAR-dA, IVRT and E-dt demonstrated only a weak but significant correlation with left ventricular end-diastolic pressures (r2dblnstlt0.25). Correlations of left ventricular end-diastolic pressures with dAR, dAR–dA, the duration of atrial reversal and duration of atrial reversal minus duration of A wave, but not E-dt, improved in patients with impaired ejection fraction or severe mitral regurgitation (r=0.47 to r=0.66). The correlation between E-dt and pulmonary venous flow diastolic deceleration time was low (r=0.2, P=0.016) and was not improved in patients with impaired ejection fraction. The linear regression of left ventricular end-diastolic pressures as dependent variable (y) on pulmonary venous flow diastolic deceleration time as measured variable (x) is shown in Fig. 4. The best non-linear regression in all patients is a hyperbola (left ventricular end-diastolic pressures = –10 + 4975/pulmonary venous flow diastolic deceleration time).


Figure 4
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  		Figure 4 Linear regression of left ventricular end-diastolic pressures as dependent variable (y) on pulmonary venous flow diastolic deceleration time as measured variable (x) with confidence intervals. From the scatter-plot it is obvious that a non-linear regression provides a better fit: left ventricular end-diastolic pressures = –10 + 4975/pulmonary venous flow diastolic deceleration time.

 
In the subgroup used for fitting (n=87), the equation was left ventricular end-diastolic pressures = –10.87 + 5261/pulmonary venous flow diastolic deceleration time. The mean difference between estimated (left ventricular end-diastolic pressures = –10.87 + 5261/pulmonary venous flow diastolic deceleration time) and measured left ventricular end-diastolic pressures in the test group was –1.3 ± mm Hg.

Pulmonary venous flow diastolic deceleration time discriminates between normal, slightly elevated and severely elevated left ventricular end-diastolic pressures. Median values and 75 and 95% data intervals in the different groups are illustrated in Fig. 5. The 75% data intervals of the three subgroups and the 95% data intervals of normal subjects and patients with severely elevated left ventricular end-diastolic pressures do not overlap. This means a nearly 100% predictive value of a severe elevation of left ventricular end-diastolic pressures as compared with normal filling pressures. A value of pulmonary venous flow diastolic deceleration time <220 ms is suggestive of elevated left ventricular end-diastolic pressures and should be monitored. A value of pulmonary venous flow diastolic deceleration time <190 ms predicts elevated left ventricular end-diastolic pressures. A value of pulmonary venous flow diastolic deceleration time <165 ms predicts severely elevated left ventricular end-diastolic pressures. If 190 ms is used as a cut-off value for elevated and 165 ms for severely elevated left ventricular end-diastolic pressures, cross-table analysis classifies all patients with normal left ventricular end-diastolic pressures correctly, misses slight elevation of left ventricular end-diastolic pressures in 28% and classifies 22% of patients with severe elevation of left ventricular end-diastolic pressures as slightly elevated. No patient with severe elevation of left ventricular end-diastolic pressures is classified as normal ({chi}2=102, P<0.0001).


Figure 5
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  		Figure 5 Box-plot of pulmonary venous flow diastolic deceleration time values grouped with respect to elevation of left ventricular end-diastolic pressures. Horizontal lines represent median values, boxes confine 75% data intervals and whiskers delimit 95% data intervals.

 
Discriminant analysis by use of pulmonary venous flow diastolic deceleration time as parameter to assess left ventricular end-diastolic pressures allowed correct classification of 80% of patients within the three groups defined with respect to elevation of left ventricular end-diastolic pressures. (Mahalonobis distance 1.94 for normal vs slightly elevated, 3.14 for normal vs severely elevated and 1.21 for slightly elevated vs severely elevated pressures P<0.0001.) The values of the discriminant function (–3.79 + 0.0173 x pulmonary venous flow diastolic deceleration time) at the group centroids is 0.73475 for normal subjects, –0.38989 for patients with slight elevation of left ventricular end-diastolic pressures and –1.08899 for those with severe elevation.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusion
 References
 
This study demonstrates that pulmonary venous flow diastolic deceleration time permits estimation of elevated left ventricular end-diastolic pressures. The fact that the study was performed in a rather large mixed population of patients with and without impaired ejection fraction adds statistical strength to this result. Pulmonary venous flow diastolic deceleration time allows patients to be stratified non-invasively with respect to normal, slightly elevated and severely elevated left ventricular end-diastolic pressures. These results agree with previous clinical studies estimating pulmonary wedge pressure or left atrial pressure in special subgroups of patients selected with respect to diagnosis and ventricular function[10–12].

We found a better correlation of pulmonary venous flow diastolic deceleration time than E-dt with left ventricular end-diastolic pressures. Similar results for pulmonary wedge pressure and left atrial pressure were found by other investigators[10–12]. The continuity principle implies that diastolic pulmonary venous forward flow increases volume of either the left atrium or the left ventricle or both. As a result, upward shifts of atrial and ventricular pressure–volume curves (decrease of compliance) limit and delay diastolic pulmonary venous forward flow and prolong filling-time. Pulmonary venous flow diastolic deceleration time is even more tightly related to diastolic left ventricular compliance than to left atrial compliance, as can be demonstrated by mathematical modelling[13]. A compliant left atrium and a compliant left ventricle in early diastole allow fast volume shifts from pulmonary veins to the left ventricle with minimal time delay and may behave like a conduit[14]. The conduit assumption is not valid in pathologic conditions and during mid and late diastole[11,12,15].

The parameters dAR–dA and dAR/dA have been related to atrial contraction and late ventricular compliance[1–4,9,16]. The parameters relating AR and A wave demonstrated a rather poor correlation with left ventricular end-diastolic pressures in our sample, which was better, however, in patients with impaired ejection fraction. This was due to an improved correlation of vAR and dAR with left ventricular end-diastolic pressures in agreement with findings of Kimura et al.[16]. A limited clinical use of dAR-dA was found by Sohn et al.[17]. Inaccuracies of dARdue to an overlap of E and A waves[18] or to insufficient image quality may occur. AR was found to be more sensitive to image quality than pulmonary venous flow diastolic deceleration time[18–20]. Regrettably direct comparisons of the correlations of left ventricular end-diastolic pressures with dAR–dA and with pulmonary venous flow diastolic deceleration time are rare[14]. We did not investigate systolic fraction of pulmonary venous flow, which was found to correlate with left ventricular end-diastolic pressures in other studies[1,2,21]. This complex parameter is influenced by systolic and diastolic left ventricular function and depends on transmitral propagation of flow and pressure in systole[21,22]. Moreover, its interpretation may be difficult in mitral regurgitation.

Limitations of the study
Left ventricular end-diastolic pressures was not assessed by tip-pressure measurements and not simultaneously with pulmonary venous flow diastolic deceleration time. The error of end-diastolic pressure in the liquid filled system is ±2 mmHg and not systematic (own unpublished measurements). Adequate images could be acquired with harmonic imaging in 95% of cases. Contrast agents may increase this number[23–26]. The exclusion of patients with mitral stenoses and mitral prostheses is not a serious limitation as in these patients haemodynamics focus on left atrial pressures, whereas left ventricular end-diastolic pressures are generally normal or low. We excluded patients with atrial fibrillation as the absent atrial contraction precludes a measurement of A and AR waves. However, pulmonary venous flow diastolic deceleration time may provide a useful estimation of left ventricular end-diastolic pressures in this group of patients[11].


   Conclusion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
References
 
Pulmonary venous flow diastolic deceleration time is an accurate, easily feasible non-invasive measurement to stratify patients in groups with a normal, slightly elevated and severely elevated left ventricular end-diastolic pressures.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Brunazzi M.C, Chirillo F, Pasqualini M, et al. Estimation of left ventricular diastolic pressures from precordial pulsed-Doppler analysis of pulmonary venous and mitral flow. Am Heart J (1994) 128(2):293–300.[CrossRef][Web of Science][Medline]
  2. Cecconi M, Manfrin M, Zanoli R, et al. Doppler echocardiographic evaluation of left ventricular end-diastolic pressure in patients with coronary artery disease. J Am Soc Echocardiogr (1996) 9(3):241–250.[CrossRef][Medline]
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  15. Hoit B.D, Gabel M. Influence of left ventricular dysfunction on the role of atrial contraction: an echocardiographic–hemodynamic study in dogs. J Am Coll Cardiol (2000) 36(5):1713–1719.[Abstract/Free Full Text]
  16. Kimura K, Murata K, Tanaka N, et al. The importance of pulmonary venous flow measurement for evaluating left ventricular end-diastolic pressure in patients with coronary artery disease in the early stage of diastolic dysfunction. J Am Soc Echocardiogr (2001) 14(10):987–993.[CrossRef][Web of Science][Medline]
  17. Sohn D.W, Choi Y.J, Oh B.H, Lee M.M, Lee Y.W. Estimation of left ventricular end-diastolic pressure with the difference in pulmonary venous and mitral A durations is limited when mitral E and A waves are overlapped. J Am Soc Echocardiogr (1999) 12(2):106–112.[CrossRef][Web of Science][Medline]
  18. Brunazzi M.C, Chirillo F, Pasqualini M, et al. Estimation of left ventricular diastolic pressures from precordial pulsed-Doppler analysis of pulmonary venous and mitral flow. Am Heart J (1994) 128(2):293–300.[CrossRef][Web of Science][Medline]
  19. Jensen J.L, Williams F.E, Beilby B.J, et al. Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique. J Am Soc Echocardiogr (1997) 10(1):60–66.[CrossRef][Web of Science][Medline]
  20. Nagano R, Masuyama T, Lee J.M, et al. Transthoracic Doppler assessment of pattern of left ventricular dysfunction in hypertensive heart disease: combined analysis of mitral and pulmonary venous flow velocity patterns. J Am Soc Echocardiogr (1994) 7(5):493–505.[Medline]
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