Comparison of Doppler Echocardiography,Color M-Mode Doppler, and Doppler Tissue

Imaging for the Estimation of PulmonaryCapillary Wedge Pressure

Francisco Gonzalez-Vilchez, MD, PhD, Jose Ayuela, MD, Miguel Ares, MD,Nuria Sanchez Mata, MD, Amparo Garcıa Gonzalez, MD, and Rafael Martın Duran, MD,

Burgos, Cantabria, and Santander, Spain

To overcome the limitations of mitral inflow param-eters for predicting pulmonary capillary wedgepressure (PCWP), combined indices (with Dopplertissue imaging or color M-mode Doppler) have beendeveloped. This study was aimed to compare theaccuracy of these indices to predict PCWP. Sixty-onepatients were studied. The best correlations withPCWP were found for indices that combined isovolu-

mic relaxation time with flow propagation velocity(color M-mode) or early diastolic velocity of thelateral mitral annulus (Doppler tissue). Both closelytracked changes in PCWP. The color M-mode-de-rived index was the most accurate in patients withnormal systolic function. (J Am Soc Echocardiogr2002;15:1245-50.)

Diastolic dysfunction increases left ventricular(LV) filling pressure and is the primary mechanismresponsible for the clinical findings of heart failure.1

Currently, Doppler echocardiography is the mostvaluable tool for the noninvasive evaluation of dia-stolic function.2 Initial efforts for the estimation ofLV filling pressure have been on the basis of theanalysis of the pulsed Doppler curve of transmitralflow. However, the mitral inflow parameters are theresult of multiple interrelated factors,3-7 which limittheir usefulness.2,8 The analysis of the pulmonaryvein flow velocities has partially improved the reli-ability of the former methods for the prediction ofLV filling pressure.9-12

Several approaches on the basis of new Dopplermodalities (color M-mode Doppler and Dopplertissue imaging) have been recently proposed asuseful methods for the evaluation of LV relax-ation.10,13-22 Combining these new parameters withthose obtained from the mitral flow curve, a moreprecise estimation of LV filling pressure has beenachieved.10,23-30

This study was aimed to compare head-to-head

the usefulness of pulmonary vein flow-, color M-mode Doppler-, and Doppler tissue imaging-derivedindices for predicting pulmonary capillary wedgepressure (PCWP).

METHODS

We enrolled 70 patients who were admitted to theintensive care department and had a balloon-tipped pul-monary artery catheter. Five patients were excluded be-cause of inadequate echocardiographic images, and 4others because of fusion of peak velocity (E) and peak latevelocity (A) waves in Doppler exploration. Four patientswith severe mitral regurgitation were included in thestudy. Thus, 61 patients (42 males and 19 females) formedthe study group. Most of the patients were in sinus rhythm(46 patients, 75%) and 43 patients (70%) were on mechan-ical ventilation. Twenty-two patients (36%) had knownischemic heart disease. The primary diagnoses were: heartfailure, 27 patients; sepsis, 6 patients; aortic valve replace-ment, 8 patients; aortic/peripheral vascular operation, 4patients; and other, 16 patients. The study was approvedby the human subjects review committees of our institu-tions.

Echocardiographic and Doppler Measurements

The studies were performed with Sonos 2500 and 5500instruments (Hewlett-Packard, Andover, Mass) equippedwith 2.5 MHz and multifrequency transducers, respec-tively, and Doppler tissue imaging. LV ejection fractionwas determined by the multiple disks method from 2-di-mensional echocardiographic images obtained from the

From the Servicios de Cardiologıa y Medicina Intensiva, HospitalGeneral Yague, Burgos; Hospital Laredo, Cantabria (M.A.); andHospital Marques Valdecilla, Santander (N.S.M., R.M.D.); Spain.Reprint requests: Francisco Gonzalez-Vilchez, Servicio de Cardio-logıa, 3a planta-Norte, Hospital Universitario Marques de Valde-cilla, Avda. Marques de Valdecilla s/n, 39008 Santander, Spain(E-mail: carvtj@humv.es).Copyright 2002 by the American Society of Echocardiography.0894-7317/2002/$35.00�0 27/4/125752doi:10.1067/mje.2002.125752

1245

apical 4-chamber view. Mitral inflow and pulmonary ve-nous curves were recorded as previously described.8 Thepulsed sample volume was placed in the area of theanterior mitral valve leaflet to capture the LV outflow tractenvelope and the mitral inflow profile simultaneously. Toobtain the propagation of early mitral inflow velocity intothe LV, the color Doppler sector map was displayed andthe M-mode cursor was positioned as parallel as possibleto the mitral inflow stream.24 Doppler tissue imaging ofthe lateral mitral annulus was obtained from the apical4-chamber view. A 0.17- to 0.51-cm pulsed volume samplewas used. All the recordings were made with a sweepspeed of 100 mm/s and stored on video tape. To assess theusefulness of new combined Doppler indices for predict-ing changes in PCWP, 16 patients were restudied afterstandard therapy, at least 24 hours after the first evalua-tion.

Measurements were done offline using the softwarepackage incorporated to echocardiographic instrumentsby an observer who had no knowledge of the hemody-namic data (F.G-V.). Five end-expiratory cardiac cycles (10cycles in cases of atrial fibrillation) were measured and theaverage used for analysis. The following parameters werederived from the transmitral velocity: E, deceleration time(DT) of E wave (DT-E), A, and E/A ratio. Isovolumicrelaxation time (IVRT) was measured from the end of theaortic flow to the onset of the mitral flow by use of pulsedwave Doppler.31 From the pulmonary vein flow tracings,we evaluated the DT of diastolic flow (DT-PV).9 As previ-ously described,24 we measured the color M-mode Dopp-ler flow propagation velocity (Vp) as the slope of the firstaliasing velocity during early filling, from the mitral valveplane to 4 cm distally into LV cavity. From the Dopplertissue recordings of lateral mitral annulus velocity, peak Ewave velocity was measured (Ea).27

The following combined indices were calculated: (1)E/Vp, as proposed by Nagueh et al23 and Garcia et al24; (2)E/Ea, as proposed by Nagueh et al27; (3) 1000/[(2 �IVRT) � Vp], as proposed by Gonzalez-Vilchez et al25; and(4) 1000/[(2 � IVRT) � Ea]. Indices 3 and 4 were derivedfrom the same theoretical background.31,32 Briefly, leftatrial pressure, time constant of LV relaxation, and IVRTare analytically related, as described by the equation32:

IVRT � � [log (pO) � log (pA)].

On the basis of this relation, we empirically derived anoninvasive index, using Vp as a surrogate for � (index3).25 Index 4 has the same rationale as index 3.

Eight studies were randomly selected to assess interob-server and intraobserver variability. The mean � SD (meanpercent error � SD) values of intraobserver variabilitywere 0.026 � 0.03 m/s (4 � 2%) for measurement of E;2 � 8 msec (10 � 7%) for IVRT; 0.025 � 0.09 m/s (14 �10%) for Vp; and 0.0035 � 0.0072 m/s (4 � 3%) for Ea.The values of interobserver variability were 0.041 � 0.07m/s (7 � 5%) for measurement of E; 2 � 8 msec (12 � 8%)for IVRT; 0.05 � 0.17 m/s (22 � 15%) for Vp; and 0.01 �0.01 m/s (13 � 13%) for Ea.

Hemodynamic Measurements

Mean PCWP was determined automatically by the moni-toring system from pressure tracings obtained with apulmonary artery catheter. Special care was taken toobtain reliable pressure tracings. All measurements wereobtained within 5 minutes of the echocardiographic ex-amination.

Statistics

Data are presented as mean value � SD. Comparisonsamong patient groups were assessed with t tests. Leastsquares linear regression analysis was chosen to correlatePCWP with echocardiographic and Doppler variables,both for the entire population and subgroups of patientswith normal (LV ejection fraction �50%) and depressed(LV ejection fraction �50%) systolic function. Differencesin the correlations between PCWP and Doppler indicesaccording to LV ejection fraction were analyzed by analy-sis of covariance. Receiver operating characteristic curveswere constructed for the combined Doppler indices andDT-PV for the prediction of PCWP �15 mm Hg. All testswere 2-tailed and the level of significance was establishedat P � .05.

RESULTS

The baseline characteristics are presented in Table1. Thirty-two patients (52%) had ejection fraction�50%. Pulmonary venous signals were adequate in36 patients (59%).

Relation of Variables to PCWP

The correlations of PCWP with Doppler variablesare shown in Table 2. The best correlations wereobtained for the indices that combined IVRT withVp or Ea {1000/[(2 � IVRT) � Vp], r � 0.88;1000/[(2 � IVRT) � Ea], r � 0.75; respectively}. Forthe latter index, the correlation with PCWP wassignificantly lower in patients with normal LV func-tion (r � 0.77) than in patients with depressed LVfunction (r � 0.93). The correlation for the colorM-mode-derived index was not affected by the statusof LV systolic function. Both E/Vp and E/Ea showedmoderate correlations with PCWP. In the 36 pa-tients with adequate pulmonary vein tracings, agood inverse correlation between DT-PV and PCWPwas observed (r � �0.79). However, a significantlybetter correlation was found in patients with de-pressed LV systolic function.

Comparison of Doppler Methods

DT-PV and the combined Doppler indices weretested to determine the accuracy of each of them foridentifying PCWP �15 mm Hg (n � 23 patients;38%). The receiver operating characteristic curvesare shown in Figure 1. The largest area was 0.98 for

Journal of the American Society of Echocardiography1246 Gonzalez-Vilchez et al October 2002

1000/[(2 � IVRT) � Vp] as compared with 0.90 forE/Vp, 0.90 for diastolic DT of pulmonary vein flow,0.85 for 1000/[(2 � IVRT) � Ea], and 0.79 for E/Ea.

Optimal cut-off value for each Doppler index wasselected according to the maximal accuracy forclassifying PCWP as normal or elevated (Table 3).The index 1000/(2 � IVRT) � Vp � 5.5 had a

positive predictive value of 95% and a negativepredictive value of 93%.

Detection of Serial Changes

Changes induced by therapy in PCWP were betterreflected by those in 1000/[(2 � IVRT) � Ea] (r �0.92; standard error of the estimate � 2.48) andthose in 1000/[(2 � IVRT) � Vp] (r � 0.84; standarderror of the estimate � 3.35) (Figure 2).

Clinical Implications

Our data showed that previously reported indices,which combine peak E wave velocity and relaxationrelated parameters (such as Vp or Ea), provide anadequate discrimination between normal and ele-vated PCWP. Nevertheless, indices that use IVRTalong with these relaxation parameters improvedthe diagnostic accuracy. Furthermore, they accu-rately tracked serial hemodynamic changes andwere easily obtained in clinical practice. A closecorrelation of 1000/[(2 � IVRT) � Vp] with PCWPremained even in patients with normal LV systolicfunction. Although DT-PV was a good estimate ofPCWP, as previously reported,9 it was difficult toacquire in all patients.

DISCUSSION

The current study shows that combining conven-tional mitral inflow parameters (E velocity or IVRT)with parameters on the basis of new Doppler mo-dalities that are related to ventricular relaxation (Vpby color M-mode Doppler or Ea by Doppler tissueimaging) provides a close prediction of PCWP. The

Table 1 Baseline characteristics

Variable

Entire

population

EF < 50%

(n � 29)

EF > 50%

(n � 32)

Age, y 68 � 11 71 � 7 66 � 13Systolic BP, mm Hg 117 � 26 115 � 29 119 � 23Diastolic BP, mm Hg 64 � 15 63 � 16 65 � 14Heart rate, bpm 98 � 19 97 � 18 100 � 20EF 47 � 19 30 � 11 63 � 7§PCWP, mm Hg 14 � 6 17 � 6 12 � 5‡E velocity, cm/sec 88 � 23 88 � 24 88 � 22A velocity, cm/sec* 78 � 30 77 � 37 79 � 23E/A* 1.2 � 0.6 1.2 � 0.7 1.1 � 0.5DT-E, msec 163 � 44 157 � 45 169 � 44IVRT, msec 73 � 20 73 � 20 73 � 21Vp, cm/s 50 � 30 31 � 12 68 � 31§Ea, cm/s 11 � 4 9 � 3 12 � 4‡DT-PV, m/sec† 164 � 45 155 � 37 173 � 34E/Vp 2.3 � 1.3 3.1 � 1.2 1.6 � 0.9§E/Ea 9.2 � 3.7 10.4 � 3.7 8.1 � 3.5‡1000/[(2 � IVRT) � Vp] 5.4 � 1.4 5.9 � 1.3 4.9 � 1.4‡1000/[(2 � IVRT) � Ea] 6.8 � 2.0 6.8 � 1.7 6.8 � 2.3

BP, blood pressure; EF, left ventricular ejection fraction; PCWP, pulmonarycapillary wedge pressure; DT-E, E wave deceleration time; IVRT, isovolu-metric relaxation time; Vp, flow velocity propagation; Ea, early diastolicvelocity of the lateral mitral annulus; DT-PV, deleceration time of thediastolic wave of pulmonary vein flow; E, early peak velocity of mitral inflow;A, peak late velocity.*Patients in sinus rhythm (n � 46).†Patients with adequate pulmonary vein flow recordings (n � 36).‡P � .05 for comparison dichotomized by EF.§P � .001 for comparison dichotomized by EF.

Table 2 Correlation (r) of Doppler indices withpulmonary capillary wedge pressure

Variable

Entire population

r (SEE, mm Hg) EF < 50% EF > 50%

E/A 0.47 (4.7) 0.64 0.24*DT-E �0.51 (5.1) �0.59 �0.41*IVRT �0.71 (4.2) �0.89 �0.66†Vp �0.34 (5.6) �0.03 �0.23Ea �0.31 (5.6) �0.05 �0.29*DT-PV �0.79 (3.9) �0.85 �0.67*E/Vp 0.50 (5.1) 0.26 0.50E/Ea 0.51 (5.1) 0.36 0.54*1000/[(2 � IVRT) � Vp] 0.88 (2.8) 0.90 0.831000/[(2 � IVRT) � Ea] 0.75 (3.9) 0.93 0.77†

A, peak late velocity; DT-E, E wave deceleration time; DT-PV, diastolicdeceleration time of pulmonary venous flow; E, early peak velocity of mitralinflow; Ea, early diastolic velocity of lateral mitral annulus; EF, left ventric-ular ejection fraction; IVRT, isovolumic relaxation time; SEE, standard errorof the estimate; Vp, flow propagation velocity.*P � .05 for comparison dichotomized by EF.†P � .001 for comparison dichotomized by EF.

Figure 1 Receiver operating characteristic curves for pre-diction of pulmonary capillary wedge pressure for Dopplerindices. DT-PV, diastolic deceleration time of pulmonaryvenous flow; E, early peak velocity of mitral inflow; Ea,early diastolic velocity of lateral mitral annulus; IVRT,isovolumic relaxation time; Vp, flow propagation velocity;AUC, area under curve (95% CI).

Journal of the American Society of EchocardiographyVolume 15 Number 10 Gonzalez-Vilchez et al 1247

index E/Vp has proved to be a valuable tool to assessLV filling pressures.23-26 Our results agree with thesefindings. Although the correlation between PCWPand E/Vp is moderate in our study, this index hasbeen useful for classifying PCWP as normal orelevated (area under curve, 0.90; accuracy, 87%).Likewise, the correlation between E/Ea and PCWPand receiver operating characteristics have beenmodest, in agreement with some studies.10 The useof IVRT along with Vp or Ea has resulted in a bettercorrelation with PCWP. In addition, these indiceshave reliably tracked serial changes in LV fillingpressures. Furthermore, 1000/[(2 � IVRT) � Vp]has consistently shown to be unaffected by LVsystolic function.25

These findings may be explained from theoreticalmodels that link tightly left atrial pressure, IVRT, and

LV relaxation.31,32 Peak E wave velocity is depen-dent on more complex determinants (ventricularrelaxation, suction, atrial and ventricular compli-ance, mitral valve inertance, and left atrial pres-sure).2-4,7

A key assumption is the relationship betweenventricular relaxation and Vp or Ea. Vp has provedto be closely related to invasive measures of relax-ation (tau).13-17,19 Moreover, the preload indepen-dence has been repeatedly reported.14,19,26 Similarly,Ea has been related to tau,20-22,33 although in a largeseries only a modest correlation was found.10 Recentreports have questioned the independence of Ea onpreload.22,26 In addition, Ea reflects local character-istics of myocardium, and the value as a globalmeasure of relaxation is controversial.10

In this study, PCWP has been used as a surrogateof mean left atrial pressure. Some studies use end-diastolic or pre-A LV pressures for similar purposes.Nevertheless, end-diastolic and pre-A pressures maynot reflect, exactly, mean left atrial pressures.34 Webelieve that mean left atrial pressure is more signif-icant from a physiopathological standpoint, and thatPCWP is more closely related to mean atrial pressurethan end-diastolic pressures. Because the theoreticalbasis of our approach is strongly related to left atrialpressure,31-32 the results of the current study couldnot be applicable for the prediction of end-diastolicLV pressure.

Study Limitations

The number of patients in this study was relativelysmall. Despite this limitation, the range of baselinehemodynamic data and ejection fraction was wide.Nevertheless, only a few patients had atrial fibrilla-tion, severe mitral regurgitation, acute myocardialinfarction, or severe LV hypertrophy. The resultsmust be taken with caution in these subsets ofpatients.

There are currently several methods that can beused to measure Vp by color M-mode Doppler. Weused that proposed by Garcia et al.24 This methoddoes not require special computer implementations

Figure 2 Comparison of predicted and observed changes inpulmonary capillary wedge pressure (PCWP) in response tostandard therapy. Dashed line and squares represent 1000/{[2 � isovolumic relaxation time (IVRT)] � flow propaga-tion velocity}; solid line and triangles represent 1000/[(2 � IVRT) � early diastolic velocity of lateral mitralannulus]. SEE, standard error of the estimate.

Table 3 Diagnostic accuracy of Doppler indices for detection of pulmonary capillary wedge pressure �15 mm Hg

Variable

S

(%)

Sp

(%)

PPV

(%)

NPV

(%)

Acc

(%)

E/A � 1.6 50 94 75 84 83DT-E � 140 msec 52 89 75 76 75IVRT � 60 msec 52 95 86 77 79DT-PV � 160 msec 93 91 87 95 92E/Vp � 2.6 74 95 89 86 87E/Ea � 8 87 66 61 89 741000/[(2 � IVRT) � Vp] � 5.5 87 97 95 93 931000/[(2 � IVRT) � Ea] � 7.25 65 92 83 81 82

A, peak late velocity; DT-E, E wave deceleration time; Acc, accuracy; DT-PV, diastolic deceleration time of pulmonary venous flow; E, early peak velocity of mitralinflow; Ea, early diastolic velocity of lateral mitral annulus; EF, left ventricular ejection fraction; IVRT, isovolumic relaxation time; NPV, negative predictivevalue; PPV, positive predictive value; S, sensitivity; SEE, standard error of the estimate; Sp, specificity; Vp, flow propagation velocity.

Journal of the American Society of Echocardiography1248 Gonzalez-Vilchez et al October 2002

but is prone to subjectivity. Our interobserver andintraobserver variabilities were within the rangereported by others.23-25 However, an automated andmore objective method19,26 would be desirable.

We only measured Ea at the lateral corner ofmitral annulus because it has been previously notedthat the lateral annulus Ea is more reproducible thanthe septal annulus Ea.27,29 Nevertheless, Ommen etal10 have recently demonstrated a better correlationbetween LV filling pressure and measurements ofthe septal annulus than that obtained with measure-ments of the lateral annulus.

The relatively low technical success of pulmonaryvein flow has been previously documented,8,10,23,29

and may be the result of examining patients undermechanical ventilation and in supine position. Wemeasured the DT-PV because this parameter hasshown the best correlation with PCWP.9,35

CONCLUSIONS

The use of indices that combine a transmitral flowparameter, especially IVRT, with a relaxation-relatedparameter (Vp by color M-mode Doppler or Ea byDoppler tissue imaging), provided a close predictionof PCWP. They accurately tracked changes in PCWP.Color M-mode Doppler-derived indices were thebest methods to assess PCWP in patients withnormal LV systolic function.

We are indebted to Dr Jose Cordero for his statisticalassistance.

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Journal of the American Society of Echocardiography1250 Gonzalez-Vilchez et al October 2002