Three-dimensional echocardiographic determination of left ventricular volumes and function by multiplane transesophageal transducer: dynamic in vitro validation and in vivo comparison with angiography and thermodilution

Three-Dimensional Echocardiographic Determination of Left Ventricular Volumes and Function by Multiplane Transesophageal Transducer: Dynamic In Vitro Validation and In Vivo Comparison with Angiography and Thermodilution Harald R Ktthl, MD, Andreas Franke, MD, Uwe janssens, MD, Marc Merx, MD, J0xgen Graf, MS, Winfi'ied Krebs, PhD, Helmut Reul, PhD, Gianter Rau, PhD, Rainer Hoffmann, MD, Heinrich G. Klues, MD, and Peter Hanrath, MD, FACC, Aachen, Germany

The goal of this study was to validate 3-dimensional e c h o c a r d i o g r a p h y by m u l t i p l a n e t r a n s e s o p h a g e a l transducer for the determination of left ventricalar volumes and ejection fraction in an i n vitr o experiment and to compare the method in vivo with b i p l a n e a n g i o g r a p h y and the continuous the r modilution method. In the dynamic i n vitr o experiment, we scanned rubber balloons in a water tank by using a pulsatile flow model. Twenty-nine measuremerits of volumes and ejection fractions w e r e p e r f o r m e d at i n c r e a s i n g h e a r t rates. Threedimensional echocardiography showed a very high accuracy for v o l u m e n i e a s u r e m e n t s a nd ejection fraction calculation ( c o r r e l a t i o n coefficient, standard e r r o r of estimate, and mean difference for endqliastolic volume 0.998, 2.3 mL, a nd 0.1 mL; for end-systolic volume 0.996, 2.7 mL, and 0.5 mL; and for ejection fraction 0.995, 1.0%, a nd -0.4%, respectively). However, w i t h i n c r e a s i n g h e a r t rate there was progressive undere stima tion o f ejection fraction calculation ( p e r c e n t e r r o r f or h e a r t rate below and above 100 b p m 0.59% a nd --8.6%, P < .001). In the in vivo study, left ventricular volumes

u . L e f t vemtricular (LV) volumes and ejection fraction (EF) have important prognostic implications. I Thus the accurate assessment of these paranaeters is of paramount importance. LV volumes have b e e n tell-

From Medical Clinic I, University. Hospital RheinischWestf~lischeTechnische Hochschulc, and Hehnholtz Institute for Biomedical Engineering,Aachen, Germany. Reprint requests: Harald P. Kiihl, MD, Medizinische Klinik I, Universit~tsklinikum der RWTtt, Pauwelstrassc 30, 52057 Aachen, Germany. E-mad: hkue@pcserve~mkl.rwth-aachen.de. Copyright 9 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 + 0 27/1/93918

and ejection fraction of 24 patients with symmetric and distorted left ventricular shape were compared with angiography results. There was good agreement f or file subgroup of patients w i t h n o r m a l left ventricular shape (mean difference • conftdence interval for end-diastolic volume 5.2 -+ 6.7 mL, P < .05; for end-systolic volume -0.5 -+ 8.4 mL, P = not significant; for ejection fraction 2.4% • 7.2%, P = not significant) and significantly m o r e variability in the patients w i t h left v e n t r i c u l a r a n e u r y s m s (enddiastolic volume 23.1 • 56.4 mL, P < .01; end-systolic volume 5.6 • 41.0 rnL, P = not significant; ejection fraction 4.9o/0 _+ 16.0%, I~ < .05). Additionally, in 20 critically ill, ventilated patients, stroke volume and cardiac output measm-ements w e r e compared with measurement from co~tinuoty~s the~inodilatiolx Stroke volume as well as cardiac output correlated well to thermodilution ( r = 0.89 and 0.84, respectively, P < .001), although both parameters w e r e significantly uaxderestimated by 3-dimensional ediocardiograpby (mean difference • confidence interval = - 6 . 4 _+ 16.0 mL a n d - 0 . 6 • 1.6 L/min, respectively, P < .005). (J Am Soc Echocarchogr 1998;11:1113 24.)

ably estimated from 2-dimensional echoeardiography in symmetric ventricles. 24 However; accuracy, precision, and reproducibility of volume measurements are p o o r in aneurysmatic LV because of the underlyhag simplified assumptions. 5s Three-dimensional echocardiography (3DE), a recently introduced imaging modality 9,10 has proven to be more accurate than conventional 1- and 2dimensional e c h o c a r d i o g r a p h i c me th o d s for th e assessment of LV volumes and function in in vitro and animal studies) 1-I5 However, only limited studies are available comparing 3DE for the assessment 1113

1 1 1 4 Ktibl et al

Journal of the American Society of Echocardiography December 1998

of the human circulatory system. Details of the model have been described previouslv22 In brief, this model generates pulsatile volume changes by volume displacement of a silicon-made flexible sac achieved by an electrohydraulic drive unit. The system allows predefiultion of various stroke vulumes (SV) and heart rates to simulate difJferem hemodyixamic conditions and cardiac output (CO) states.The simulated heart rate was changed from 50 to i 8 0 bpm. Symmetric rubber balloon phantoms failed with known volumes were colmected to the model and scanned in a water bath.True volumes ranged from 48 to 220 m L A total of 29 separate measurements were performed in 9 different simulated hemodyrmmm gates.Figure 1 shows an illustration of file pulsaEie flow model with the balloon phantom In the water bath. I n Vivo S t u d y : B i p l a n e A n g i o g r a p h y

F i g u r e 1 Schemarac dra,Mng ofpulsatile flow model (r~h~) with balloon p h a n t o m in water bath and muitiplane trans esophageal echocardiographic transducer (left:). 1, Piston; 2, balloon p h a n t o m ; 3, nmltiplane transesophageal echocardingraphic transducer; 4, fluid-filled water bath; N compressible silicone-made sac; 6, filler pipe.

o f t h e s e p a r a m e t e r s in a l a r g e r s e r i e s o f patients.t6-20 Most investigators have focused on methods that use t r a n s t h o r a c i c i m a g e a c q u i s i t i o n . T h e m a j o r disadvant a g e o f t h e s e m e t h o d s is t h e l i m i t e d t r a n s t h o r a c i c i m a g e q u a l i t y in a p p r o x i m a t e l y 10% to 15% o f p a t i e n t s n o t s u i t a b l e for t h i s t e c h n i q u e . M o r e o v e r , these methods require spacious equipment, which impedes transportability. Multiplane transesophageal e c h o c a r d i o g r a p h y (TEE) h a s t h e p o t e n t i a l t o overc o m e t h e s e l i m i t a t i o n s , p r o v i d i n g a nearly" u n o b structed view of the heart. The combination of mult i p l a n e TEE a n d 3 - d i m e n s i o n a l r e c o n s t r u c t i o n m a y a l l o w a n a c c u r a t e d e t e r m i n a t i o n o f LV v o l u m e s a n d f u n c t i o n , e s p e c i a l l y in p a t i e n t s w i t h a s u b o p t i m a l transttloracic imaging window. W e h a v e r e c e n t l y s h o w n t h a t 3DE w i t h muitipLane TEE is a n a c c u r a t e a n d h i g h l y r e p r o d u c i b l e m e t h o d for tile in vitro d e t e r m i n a t i o n of v o l u m e s o f n o r m a l a n d d i s t o r t e d LV casts. 2t C o n s e q u e n t l y , it w a s t h e a i m o f t h i s s t u d y to (1) validate t h e a c c u r a c y o f 3DE for t h e a s s e s s m e n t o f v o l u m e s a n d EF in a d y n a m i c i n vitro m o d e l a n d (2) p e r f o r m a n in vivo c o m p a r i s o n to biplane angiography and continuous thermodilution.

METHODS

For the comparison to biplane angiography, 24 patients with k n o w n or suspected coronary artery disease and dinical indication for left heart catheterization w e r e Included. Informed consent from each patient and ethics committee approval were obtained.The mean age was 56 -+ 10 years (range 38 to 72 years), mid 21 (88%) were men. SLxteen patients had LV aneurysms w i t h severe distortion of LV geometry caused by previous myocardial infarction (anterior wall aneurysm in 10, posterior or posterolateral wall aneurysm In 4, and apical aneurysm in 2 patients). Eight patients had normal LV shape and flraction. Significant cordnmT artery disease could be excluded ha 3 patients. 3DE was performed within 1 w e e k of (ardiac catheterization (mean 2.0 -+ 2-3 days). Heart rate was not different between the 2 studies (73 +- 12 b p m during angiography and 76 _+ 11 b p m during echocardiography;P = not significant iNS]). Cardiac catheterization and ventriculography were performed according to standard Judldns technique w i t h a Siemens biplane angiographic system (Hi-Core, Siemens, Eriangen, Germany). Cineventriculograms were recorded at 25 frames/s during p o w e r Injection of 35 mL of contrast agent at 15 mL/s from standard right anterior oblique 30 degree and left anterior oblique 60 degree projections.The magnification factor of each projection was determined by filming a metallic sphere of k n o w n dimensions at the level of the midventricle. Only sinus beats not preceded by a premature beat were selected for analysis. After end-systolic and end-diastolic frame selection, the single images w e r e digitized for semiautomatic data analysis (A\VOS, Siemens; Erlangen, Germany). Ventricular contours were manually traced and papillary muscles were included in volume measurements. End
I n V i t r o Study: E x p e r i m e n t a l S e t u p

Continuous Thermodilution

All experiments were performed in an electroh~xtraullc computer-controlled pulsatile flow model simulating the left side

For the c o m p a r i s o n to the c o n t i n u o u s t h e r m o d i l u t i o n method~ 20 patients (mean age 64 -+ 10 years, 75% men)

Journa] of the American Society of Echocardiography Volume II Number 12

admitted to the intensive care unit for cardiogenic shock associated with acute myocardial infarction (anterior wall in 10 and posterior wall in 4 patients), severe congestive heart failure (3 patients), and cardiopulmonary resuscitation (3 patients) w e r e included. All patients required lnecllahieal ventilation. Intravenous catecholamines were continuously infused in all patients, and an intla-aortic balloon p u m p was administered to 13 (65%) patients. Multiplane TEE was performed after hemodynamic stabilization. Patients with significant m i t ~ l or aortic regurgitation (>__2+) as well as significant tricuspid regurgitation and intracardiac shunt as judged by Doppler echocardiography were excluded from the study. All patients were in sinus rhytilm Mean beart rate was 94.8 • 16.8 bpm and was stable dulS~g the rotational scan. Mean heart rate variability was 2.6 -+ 3.0 bpm (2.8%) during the sVddy. A modified Swan-Ganz c a t h e t e r (Intellicath, Baxter Edwards Critical Care; 1trine, Calit) with a thermal filament was introduced into the right pulmonary artery through a 9F sheath inserted into the internal-jugular vein.The correct position of the catheter was conf'trmed by a chest roentgenogram.The catheter was connected to a specially designed c o m p u t e r (Vigilance, Baxter Edwards Critical Care). The technique has been described previously. 24 In brief, low energy applied to the filament is transformed into heat arid transmitted to the surrounding blood.The computer cross-correlates tile energy input with the temperature change detected by the thermistor at tile catheter tip to reconstruct a thermodihition curve.The CO is estimated every 30 to 60 seconds, and an average value is displayed on the screen every few minutes. Three-dimensional Echocardfography E c h o c a r d i o g r a p h i c T e c h n i q u e a n d D a t a AcqLtisition. A detailed description of the 3-dimensional system has been published previously. 25,26 In brief, echocardiographic studies were performed with a Sonos 2500 echo machine (Hewlett-t~ackard, Andover, Mass). All patients were mildly sedated during the echocardiographic study, and all patients were ha sinus rhythm. Data acquisition was performed from the esophageal probe position because of the wen-known difficulties in including the apex from the transgastric transducer location. Great care was taken to completely visualize the left ventricle from an optimal transesophageal window. This included adequate retroflexion and side angulation of the probe to optimally position the left ventricle ha the center of tile imaging sector. Tltis ensured inclusion of the apex of the left ventricle even in patients with apical aneurysms dnrJDg the rotational scan. The ttmasducer position and manual adjusLq3ent of steering wheels were kept constant during data acquisition. Data acquisition was performed by using all mmmdifled, commercially available muifiplane probe (6.2 MHz, 64 eleme~ats; Hewlett-Packard) and tile 3-dimensional acquisi-

I(i~hl et al 1115

tion software implemented in the echo machine. Image acquisition was triggered by electrocardiographic and impedance-based respiratory gating.A complete scan consisted of 90 sequential cross sections at 2 degree intervals from 0 to 180 degrees. Mean duration of the data acquisition was 4.3 -+ 2.4 minutes.After data acquisition, the 3dimensional raw data were processed off-line (EchoScan, TomTee, Munich, Germany). Data sets were stored on a magneto-optical disk for off-line analysis. D a t a Analysis. Analysis was performed by 2 independent observers. The true long axis was defined in the s)mametric rubber balloon phantoms and the reconstructed le~t ventricles in the 3-dimensional data set. In the in vivo study, the reconstructed cross section showing the maximal distance from mitral annulus to apex was selected. In this cross section, the true inng axis of the reconstructed left ventricle was determined by connecting the center of the mitral annulus and the apex of the left ventricle. Thereafter, parallel short-axis slices of 5 m m thickness (1 mm for the analysis of the phantoms in the in vitro study) perpendicular to ttle long axis were created in the data set, and the volume of each slice was calculated after manual contour tracing.Total EDV and ESV were displayed after automatic summation of slices. In the in vitro study, EDV and ESV were measured in the frame showing maximal balloon expansion and contraction, respectively. For the in vivo studies, the EDV was nleasured in the frame after mitral valve closure and the ESV after aortic valve closure. EF was calculated as 0EDV - ESV)/EDV * 100. Statistical A n a l y s i s All values are given as mean _+ SD unless otherwise specified. Linear regressio~ analysis was used to compare volumes and EF, SV, and CO ha in vitro as well as in vivo studies. The limits of agreement b e t w e e n pairs of measurements were determined according to the method described by Bland aildAltman, z7 Differences between the means were assessed by nonparametric matched-pairs test OWilcoxon signed rank test). To assess the measurement error of EF calculation depending on heart rate in file in vitro study, w e plot-ted the p e r c e n t error [(measured value - true value)/true value)] against tile simulated heart rate.The mean percent error for heart rates above and below i 0 0 bpm was compared by use of the unpaired t test. Linear regression analysis and Spearman rank correlation coefficient were used to determine whether the percent error varied significantly with heart rates above and beiow 100 bpm. Observer variability- was obtained by calculating the difference between 2 consecutive measurements from the same observer and between measurements from 2 independent observers. Values were expressed as percent of the first measurement and as the standard deviation of the differences of 2 measurements given in parentheses For

lournal of the American Socicty of Echocardiography December 1998

1116 Ktilil et al

EDV and 250

ESV (ml) 10

200 -

150-

o .w.9 --...~-. 9 9.~, .~..-.~-

-..--~-.."

ill 100-

o

/

S0-

mean bias . . . . .

-,0/ 5~)

A

1;0 ' 150 True Values (ml)

I 200

250

Ejection 5O

~ IJ

,

,100

0

/X EDV= 0.1ml

~176 150

Fraction 6

[]

oo

O 30 -

,,o,

250

(%)

12

40-

200

True Values (ml)

9 [~ . . . . . [] []

uJ ~-2 20-

~.. []

[]

mean bias=-0.4% -6

2~

Ct0

3~

20

s0

True Values (%)

D

10

210

3~) True Values (%)

410

50

Figure 2 Restdts of in vitro study. A and C, Linear regression analysis between 3-dimensional echocardiography and true values for end diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF), respectively. B and D, Bland Alunan analysis of differences for same parameters as in A and C. Dotted lines represent mean difference (mean bias). Diff difference. the in vitro study, all 29 measurements were repeated by the same observer and by a blinded independent observer. Similarly,for the in vivo study, LVEDV and ESV ~nd EF were reassessed in 10 randomly selected patients.

RESULTS In Vitro Validation T h e individual values for each experimental setup are sunlmarized inTable 1.Table 2 gives the results of the regression analysis and the limits of agreement comparison of 3-dimensinnal measurements to true values. Figure 2 (A through D) shows linear regression analysis and Bland-Airman plots for EDV,ESV,and EF calculation.

The r e was excellent agreement b e t w e e n LV volumes and EF d e t e r m i n e d by 3DE and true values with high correlation coefficients and lo w standard error of estimate (SEE) (<3 mL). Bland-Akman analysis revealed no systematic error and equal distribution of the differences for the whole range of values. The greatest differences (>3 mL) w e r e observed at heart rates of at least 100 bpm. The measurement error for EF calculation depending on heart rate is shown in Figure 3. In the u p p e r panel, the averaged results of 2 i n d e p e n d e n t observers are shown; in the lower panel, their individual results are depicted. For both observers, there is increased measurement variability and a progressive underestimation of EF calculation w i t h heart rates of more than 100 b p m . T h e average mean per-

Journal of the American Society of Echocardiography Volume l I Number 12

Ktibl et al 1 1 1 7

T a b l e 1 In vitro study: Individual values No.

HR

EDVT~e (mL)

ESVT~ (mL)

EFT~ (%)

EDV3D(mL)

ESV31 ) (mL)

EF3D(%)

% Error

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

50 50 50 50 60 60 60 70 70 70 80 80 80 100 100 100 100 100 t00 100 120 120 I20 150 150 150 180 180 180

80 80 80 80 150 150 150 220 220 220 150 150 150 85 85 85 85 150 150 150 140 140 140 140 140 140 140 140 140

48 48 48 48 90 90 90 140 140 140 90 90 90 48 48 48 48 90 90 90 110 110 110 110 110 110 110 110 110

40 40 40 40 40 40 40 36.4 36.4 36.4 40 40 40 43.5 43.5 43.5 43.5 40 40 40 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4 21.4

78.3 78.9 81.8 81.4 150.2 151.1 149.9 220.9 220.9 219.2 150.1 151.7 151.6 83.3 87.4 86.9 86.3 148.8 152.0 I49.1 136.9 135.1 137.8 136.5 136.5 I35.5 144.1 139.2 139.8

46.4 46.8 49.0 49.8 89.3 90.2 89.8 141.9 141.9 140.6 89.0 88,4 91.2 47.6 48.7 47.9 47.2 88.9 89.1 91.0 111.0 109.4 106.9 109.1 112.0 106.3 118.3 115.4 115.3

40.7 40.7 40.1 38.9 40.5 40.3 40.1 35.8 35.8 35.9 40.7 41.7 39.9 42.9 44.2 44.9 45.3 40.3 41.4 39.9 18.9 19.0 22.4 20.0 17.9 21.5 17.9 17.1 17.5

1.7 1.7 0.2 5.7 4.0 -1.1 0.4 1.3 -1.5 1.5 -1.3 1.2 0.7 0.2 1.07 4.2 ~0.2 0.7 3.05 0.2 11.8 -11.3 4.05 ~5.7 -16.5 0.3 -16.5 -20.2 -18.3

MR, Heart rate; EDV, end-diastolicvolume; ESV,,end systolicvolume; EF, ejection ~acfion; %Error, percent error of ejecnon fraction calculation; Tr~e,true values; 3D, 3 dimensiona2echocardiography.

c e n t e r r o r f o r h e a r t r ates less t h a n o r e q u a l t o 1 0 0 b p m w a s 0 . 5 9 % -+ 2.0% a n d for h e a r t rat e s m o r e t h a n 1 0 0 b p m - 8 . 6 % -+ 6 . 1 % . T h i s d i f f e r e n c e w a s statisticaUy s i g n i f i c a n t ( P < . 0 0 1 ) . W i t h i n c r e a s i n g h e a r t rate of more than 100 bpm, we found a progressive u n d e r e s t i m a t i o n o f EF c a l c u l a t i o n b y 3DE ( F i g u r e 3). Comparison

to biplane

angiography

F i g u r e 4 s h o w s a diastolic (left) a n d systolic (right) longitudinal cross section from the 3-dimensional data set of a patient with an apical aneurysm. Linear r e g r e s s i o n analysis a n d B l a n d - A l t m a n p l o t s for symm e t r i c a n d a n e u r y s m a t i c left v e n t r i c l e s are s h o w n i n F i g u r e 5 (A t h r o u g h D ) . T a b l e 3 gi ve s t h e m e a n s a n d s t a n d a r d d e v i a t i o n s for t h e p a r a m e t e r s i n v e s t i g a t e d . F o r t h e w h o l e s t u d y g r o u p , i n c l u d i n g s y m m e t r i c as w e l l as a n e u r y s m a t i c left v e n t r i c l e , e c h o c a r d i o g r a p h ic EDV,, ESV, a n d EF c o r r e l a t e d w e l l t o t h e v a l u e s obtained by cineventriculography. Subanalysis of p a t i e n t s w i t h s y m m e t r i c left v e n t r i c l e s r e v e a l e d h i g h c o r r e l a t i o n c o e f f i c i e n t s a n d l o w SEE for v o l u m e s a n d EE F o r p a t i e n t s w i t h d i s t o r t e d LV s h a p e , l o w e r c o r r e l a t i o n c o e f f i c i e n t s a n d l a r g e r SEE w e r e f o u n d (Table

2). 3DE s i g n i f i c a n t l y u n d e r e s t i m a t e d c i n e v e n t r i c u l o g r a p h i c EDV i n b o t h p a t i e n t g r o u p s , a l t h o u g h less for t h e s u b g r o u p o f p a t i e n t s w i t h s y m m e t r i c left ventricles ( m e a n d i f f e r e n c e 5.2 v s 23.1 mL). EF c a l c u l a t e d by 3DE was significantly lower compared with r e s u l t s b y a n g i o g r a p h y i n a n e u r y s m a t i c left v e n t r i c l e s ( m e a n d i f f e r e n c e 4 . 9 % , P < .05), a n d t h i s differe n c e w a s n o t sthtistically s i g n i f i c a n t f o r s y m m e t r i c left v e n t r i c l e s ( m e a n d i f f e r e n c e 2.4%, P = NS). F o r ESV, t h e d i f f e r e n c e b e t w e e n t h e m e t h o d s w a s n o t statisticaUy significant. Comparison

to Continuous

Thermodilution

T h e r e s u l t s o f C O a n d SV c a l c u l a t i o n b y c o n t i n u o u s thermodihition are summarized in Figure 6 and T a b l e s 2 a n d 4. M e a n v a r i a t i o n i n t h e r m o d i l n t i o n C O measurements during the study was 0.21 L/rain ( r a n g e 0.0 t o 0.51/rain), c o r r e s p o n d i n g t o 4.3% o f t h e m e a n CO. There was a good correlation between the 2 metho d s f o r b o t h c a r d i a c o u t p u t d e t e r m i n a t i o n ( r = 0.84; P < , 001) a n d SV c a l c u l a t i o n ( r = 0.89; P < .001). Analysis o f t h e l i m i t s o f a g r e e m e n t s h o w e d t h a t 3 D E

Journal of the Aanerican Society of Echocardio~aphy December 1998

1 1 1 8 Kiihl et al

Table 2 Statistical results of in vitro study in ptilsatile model and in vivo comparison o f 3 dimensional echocardiography to cineangiography and thermodilution P value for

Study

l=~ramet~

n

In xdtro comparison (pulsatile model)

EDV (mL) ESV (mL) EF (%) % Er <100 bpm % Er >100 bpm

29 29 29 20 9

EDV (mL) ESV (mL) EF (%) EDV (mL) ESV (mL) EF (%) EDV (mL) ESV (mL) EF (%) SV (mL) CO (L/rain) CI (L/min/m 2)

24 24 24 8 8 8 16 i6 I6 20 20 20

In ~4vo comparison to cineangiography All

Sym

Any

In vivo comparison to thermodilution

SEE

Regrlsssion equation

Mean difference

0.998 0.996 0.995 -0.08* 0.95*

2.3 2.7 1.0 2.0 2.6

y = 0.99x + 1.4 y = 1.02x- 1.3 y 1.10x- 3.9 y = 0.0Ix + 1.1 y = 0.21x + 23.6

0.90 0.94 0.93 0.98 0.97 0.92 0.86 0,90 0.72 0.89 0.84 0.80

23.9 17.2 7.0 3.4 3.9 3.1 28.8 21.2 7.5 7.8 0.7 0.4

y 0.87x + 2.2 y= 0.96x 0.6 y = 0.96x 2.0 y 0 . 9 7 x - 2.3 y 0.89x+ 4.3 y 0.75x + I4.7 y - 0.91x - 8.8 y - 1.02x 7.5 y = 0.69x + 7.4 y - 0.86x + 0.7 y - 0.74x + 0.6 y 0.69x + 0.4

Limits of ~gr~ment

difference of m ~ *

0.I 4.6 NS 0.5 5.4 N5 0.4 2.8 N5 . . . . . . . . . . . . . . . . . .

17.2 3.5 4.0 5.2 0,5 2,4 23,i 5.6 4.9 6,4 0,6 -0,3

48.0 34 13.8 6.7 8.4 7.2 56.4 41.0 16.0 16.0 1.6 0.8

.001 NS <.05 <.05 NS NS <.01 NS <.05 <.005 <.005 .005

SEE,Standard error of estimate;EDV,endLdiastolicvolume; ESV, end ~,stolicvolume; EF, ejectionfraction; %Er 100 b2m, percent error of ejection fraction calculationfor heart rotes >I 00 bpm; Sym, symmetric;Any, aneurysmafic;SV, s~oke volume; CO. cardiac output; CI, cardiacindex; NS, not slgditi~nt. *Spearm~ rank correlation coefficient, tP value for difference of means between 3-dimensional echoc~ddogmphy and reference method.

Table 3 Mean values and standard deviation for comparison to biplane angiograpby Patients All

Symmetric LV

Aneurysmatic LV

Parameter

3-nimellsional ~ h o

Biplane angiograplly

P value

EDV (mL) ESV (mL) EF (%) EDV (mL) ESV (mL) EF (%) EDV (mL) ESV (niL) EF (%)

133.5 • 53.6 77.6 ~ 49.7 45.4 • 18.2 108.2 -+43.6 36.4 • i7.3 67.0 • 7.2 146.2 • 54.8 98.2 -+47.8 34.6 -+ 10.5

I50.7 • 55.3 81.2 + 48.5 49.4 • 17.5 113.5 _+44.6 35.9 • 18.9 69.4 + 8.8 169.3 -+ 51.6 103.7 + 42.4 39.5 -+ 10.9

.001 NS <.05 <.05 NS NS <.01 NS <.05

LV, Le~ wnzaicle;EDE end-diastolic volume; ESV,end systolicvolume; NS, not significant.

significantly u n d e r e s t h n a t e d C O b y a m e a n of - 0 . 6 _+ 0.8 L / r a i n ( P < . 0 0 5 ) a n d SV b y a m e a n o f - 6 . 4 _+ 8 . 0 n i l ( P < .005) c o m p a r e d w i t h t h e c o n t i n n o u s therm o d i h i t i o n m e t h o d (Table 2). Observer Variability For t h e i n vitro study, i n t r a o b s e r v e r variability w a s 1.9% ( 1 . 8 mL) for v o l u m e m e a s u r e m e n t s a n d 4.6% (1.0%) for EF c a l c u l a t i o n . I n t e r o b s e r v e r v a r i a b i l i t y w a s 1.8% ( 1 . 4 mL) a n d 4.8% (1.2%), respectively. For t h e i n vivo study, i n t r a o b s e r v e r variability w a s 4.1% ( 3 . 4 mL) for v o l u m e m e a s u r e m e n t s a n d 9.8% (3.3%) for EF calculation. I n t e r o b s e r v e r variability" w a s 4.4% (3.8 mL) a n d 11.1% (3.7%), respectively.

DISCUSSION

This s t u d y c o n s i s t e d o f 2 parts. In t h e first part, w e d e m o n s t r a t e d in a n in vitro e x p e r i m e n t s i m u l a t i n g a b e a t i n g h e a r t t h a t m u l t i p l a n e TEE c o m b i n e d w i t h 3d i m e n s i o n a l r e c o n s t r u c t i o n a l l o w s a c c u r a t e llleas u r e m e n t o f v o l u m e s a n d EE H o w e v e r , a p r o g r e s s i v e u n d e r e s t i m a t i o n o f EF c a l c u l a t i o n w i t h i n c r e a s i n g h e a r t r a t e o f m o r e t h a n 100 b p m c o u l d b e d e m o n s t r a t e d . T h u s a c c u r a c y o f 3 D E is l i m i t e d a t h i g h e r h e a r t rates. In t h e s e c o n d part, w e a p p l i e d t h e p r e v i o u s l y valid a t e d 3DE m e t h o d i n a n in vivo clinical s e t t i n g . T h e

Journal of the American Societyof Echocardiography Volume 11 Number 12

Kfihl et al 3.119

Table 4 Mean values and standard deviation for compali-

son to continuous rhermodilafion Par~ete~

SV (mL) CO (L/min) CI (L/minim 2)

3-Dimensional echo

Continuous ther modiluUon

P value

46.4 • 16.8 4.3 -+ 1.3 2.2 -+0.6

52.8 + 17.3 4.9 -+1.5 2.5 • 0.7

<.005 <.005 .005

0 O.

--g-g ~ o

0 o o

0

O

0 0 o

SV,Strokevolume;CO,c~diacoutput; CI, cardiacindex.

o 0

-10.

results of 3DE volume measurements and EF calculation were compared with results obtained by biplane angiography in patients with normal and distorted LV shape. A high agreement between tile 2 methods could be demonstrated for patients with symmetric LV shape. However, in patients with LV aneurysms, agreement was lower because of the inaccuracies of the angiographic method to accurately describe LV geometry. Furthermore, in critically ill, mechanically ventilated patients, we compared CO and SV assessed by 3DE with measurements obtained invasively by the continuous CO method. Although correlation between the 2 methods was reasonable, a significant underesthrtation of both parameters by the echocardiographic method could be demonstrated.

-20 40

I

E

80

100

I

I

I

I

120

140

t60

180

i 160

180

200

Heart Rate

.~

10.

u.= o

~

-11

e

o -20, O Observer 1

Methodologic Considerations Two-dimensional echocardiographie methods have been proven to be of limited value for the accurate assessment of LV volumes in the presence of distortion of LV geometry, for example, aneurysm formation, because of simplified geometric assumptions that do not accurately describe the complex shape of the left ventricle in the presence of distortion. 5-s However, this problem is not unique to 2-dimensional echocardiography but is also true for other imaging techniques, such as angiography, which rely on the description of the shape of the left ventricle in only 2 dimensions. In contrast, 3DE has been shown to overcome these limitations because determination of LV volumes can be done without assumptions on LV shape. Currently, transthoracic 3DE has been used most widely for the assessment of LV volumes and function. However, this approach has important drawbacks that may limit its clinical applicability in approximately 10% to 15% of patients because of a restricted transthoracic echo window. Difficulty in including the whole apex into the imaging sector may be a particular problem in patients with apical aneurysms when the apical rotational approach for 3-dimensional reconstruction is used. 16 Moreover, in critically ifi, mechanically ventilated patients in the

I

60

Observer 2

~0 40

= 60

i 80

i 100

i i 120 140 Hea~Rate

I

200

Figure 3 Heart rate dependent underestimation of ejec tion fraction calculation by 3-dimensional echocardiography in pulsatile in vitro model. Upper panel, Averaged values for 2 independent observers; lower panel, individual values for 2 independent observers.

intensive care unit, this method is not applicable because of the unfavorable supine position of the patient and the intervening lung tissue with every mechanically induced inspiration. However, it is especially in this subgroup of patients in w h o m accurate assessment of cardiac function is of utmost importance for therapeutic decision making and for prognostic reasons. Furthermore, another limitation of the currently available transthoracic 3DE systems has been the need for special modifications of the imaging system with spacial locating or holding devices m o u n t e d on the transducer that limit its transportability. Therefore, these methods are not ubiquitously available and are currently restricted to the echo lab. With TEE, many" of the above-mentioned limitations are overcome. The anatomy" of the esophagus

1120 Kfihl et al

Journal of the American Sodcty of Echocardiography December 1998

Figure 4 End-diastolic (left) and end systolic (right) stop-flame images of aneurysmafic left ventricle reconstructed from 3-dimensional echocardiographic data set. Arrows point to apical left ventricular aneurysrn.

offers a predefined, relatively stable imaging platform that facilitates a nearly tmobstructed view on the heart with excellent image quality. 28 With the use of a multiplane transducer, the whole heart is easily imaged during a rotational scan, including the apex and the true long axis, even in ventricles with aneurysms and distorted LV geometry. Moreover, acquisition of 3Mimensional data sets with TEE is possible with commercially available unmodified echo transducers. This ensures mobility, a prerequisite for the introduction of 3DE into the intensive care unit and operating rooms, C o m p a r i s o n t o I n Vitro s t u d i e s Previous studies have extensively validated statical volume measurements from 3-dimensional reconstruction of symmetric balloon phantoms and abnormally shaped casts of left ventricles at necropsy. liq4,29-32 In this study, we have extended the experimental setup to a unique dynamic flow model.Therefore, this is the first study to validate in an in vitro setting the accuracy of 3DE for volume measurements and EF calculation in the simulated beating heart. Currently, one of the major drawbacks of echocardiography is its limited temporal resolution because of the fixed frame rate of the video signal, that is, 25 to 30 frames per second, depending on the video system used. With increasing heart iate and shortening of the cardiac cycle, only a limited number of video frames will be available for analysis, which may be insufficient to capture true end
tion of ESV and underestimation of ED~ In our experiment, we observed that the measurement error of EF associated with heart rates up to 100 b p m is acceptably low w i t h o u t any trend toward underestimation or overestimation, but that there is progressive underestimation of EF calculation with heart rates of more than 100 bpm.Therefore, accurate assessment of EF by 3DE is limited at higher heart rates. However, this problem is not particular to echocardiography but affects all other imaging techniques as well, such as angiography and magnetic resonance imaging, wllich are equally dependent on a fixed frame rate. C o m p a r i s o n t o I n Vivo Studies Previous studies with 3DE have demonstrated the high accuracy of file method in experimental animal models, including normal ventricular geometry and aneurysmatic left ventricles.14,15 However, there is only a lhnited number of studies that have applied 3DE for volume calculation and cardiac function in a larger series of patients. 1620 Recently, the high accuracy of transthoracic 3DE with an apical rotational approach for the assessment of LV volumes and function in patients with LV aneurysms was reported by Buck et al. 16 In this study, underestimation of LV volumes was reported ia some cases because of limited delineation of large apical aneurysms in the coneshaped reconstruction of the data set. In contrast, in our study with 3DE and multiplane TEE, no patient had to be excluded because of inadequate visualization of the LV apex from the transesophageal position.There are 2 studies that compared the determi-

Journal of the American Sodety of Echocardiography Volume 11 Number 12

I(fihl et al 1121

EDV and

(ml) 100-

ESV

300 9

A /~A

200.

A ~

A

9 -_A__.X4L-__

A_

.

.

.

.

.

0.~

Lu 100-

/ ~ :

~

~L,

A Any-EDV

"

~s~

Azx

~ .,0. m e a n bias

9 Sym-EDV

- - -

EDV AIl=17.2ml

......

O Sym-ESV 100

A

I

200

300

Cineangiography (rnl)

-100

B

ESV AIl=3.Sml

i

i

100

200

300

Cineangiography (ml)

Ejection Fraction (%) 100

30

2o

80-

0 O0

O0

9

60o

i

40-

20-

~

0

-20 mean

C

i 20

i l 40 60 Cineangiography (%)

i 80

-3O 100

D

2~

CD@~

bias - - - O Any = 4,9% . . . . . . 9 Sym = 2.4%

4~

s;

Cineangiography (%)

,~

100

Figure 5 Results of in vivo comparison to biplane angiography. A and C, Linear regression analysis between 3 dimensional echocardiography and biplane angiography for end-diastolic volume (ZDV), and systolic volume (ESV), and ejection fraction (EF), respectively. B and D, Bland Akrnan analysis of differences for same parameters as in A and B. Do~r linesrepresear mean difference (mean bias). Dif3~, difference; Any~ aneurysmafic left ventricle; Sym~symmetric left ventricle.

nation of LV EF from transthoracic 3DE with radionoclide angiography, both showing good agreement between the 2 methods. 19,z~In both studies, EF was the evaluated parameter. However, EF is known to be more tolerant of volume errors than absolute volumes. Furthermore, Nosir et al z~ included only patients with good transthoracic image quality. Recently, Sapin et a117 compared the results of transthoracic 5DE determination of LV volttmes and EF with the results of single-plane cineventriculograplay in nonselected patients referred for coronary angiography.They found a high agreement between

the 2 methods. In comparison to their results, we found rather lower correlation coefficients and larger limits of agreement for EDV and ESV in our study population. This may- be the result of differences in the patient population because more patients with severely distorted LV geometry were included in our study. Furthermore, we found a higher correlation coefficient for EF calculation between 3DE and angiography that may be explained by the use of biplane instead of monoplane angiography as the reference method. Our results compare favorably with the study by Hozumi et al.18 Similar to our study, they

Journal of the American Societyof Echocardiography December 1998

1122 Kiihl et al

C a r d i a c O u t p u t (l/min)

7

o ,?, 0

6

s 4

i 3

A

u 4

i 5

mean E

2

.o_ *~

1

0 -,

o

u 6

/ 7

i 8

Thermodilution (llmin)

9

_,_+1__,___ 9 ~ ~%" . . . . . . . . 9

-2

.~

bias=-O.61/min

9 9

-3 B

Thermodilution (l/min)

Figitre 6 Results ofh~ vivo comparison to continuous thor modilution. Linear regression and Bland Akman analysisof differences between 3-dimensional echocardiography and thermodiludon for cardiac output determination.

used a multiplane transesophageal transducer and compared the results of volume and EF determination with the results from biplane angiography. Comparison to Continuous T h e r m o d i l u t i o n Method Determination of cardiac function in critically ill patients is of exceptional importance because it is a powerful prognostic parameter. Currently, assessment of LVffmction in this patient group is performed invasively with a SwanXT~anz catheter. However, the invasive nature of this technique is fraught with hazards and complications, and its widespread use in a noncardiac patient population has recently been under debate. 33 Moreover, this method does not provide

any information regarding cardiac chamber volumes, the degree of impairment of LV function, the regional distribution of wall motion abnormalities, and associated cardiac pathologies such as valvular heart disease. In contrast, echocardiography is a powerful tool to address these issues. In this study we found 3DE with multiplane TEE to be a fairly accurate method to determine CO and SV in a critically ill, mechanically ventilated patient population compared with thermodilution measurements. We chose the continuous thermodiintion method because of a higher accuracy and a greater resistance to thermal noise compared with the traditional intermittent bolus injection method. 34 Moreover, this approach allows a true simultaneous comparison of the 2 methods investigated.It is independent from the operator, and volume overload by multiple injections is prevented. Furthermore, errors associated with variations during the respiratory cycle are avoided. Measurement of SV with the use of 3DE In comparison to thermodiintion has been reported first by Martin and Bashain 35,36 in experimental animals. Recentl); Mtiller et al37 evaluated SV and CO measurements in a small series of 12 patients after coronary artery bypass surgery with transesophageal 3DE and compare d the results with that of the intermittent intravenous bolus thermodilution method. 37 They found a good correlation & = 0.95) for SV determination in a subgroup of 9 patients with constant heart rate, although overall correlation was lower (r = 0.78) for the whole study group. Similar to the results in our study, they observed sigxlificanfly lower values for CO and SV measurements by the echocardiographic technique. They attributed this result to the low temporal resolution of the 3DE method. However, it has been demonstrated in in vitro ewperhnents that tllermodilution overestimates CO determination, especially in conditions with low flow rates.38 Furthermore, significant differences of thermodilution CO measurements compared with other validated methods (ie, oxygen consumption-based methods) for the determination of CO have been observed in clinical studies. 39 Although widely validated, thermodilntion methods are known to lack accuracy, especially in the upper and lower parts of the CO spectrum. We therefore believe that the differences observed in comparison to the 3DE method may have been partially caused by the inaccuracies of the reference method itself in this selected patient population with low cardiac output. L i m i t a t i o n s a n d Sources o f E r r o r I n Vitro Study. In our dynamic in vitro study, we used only symmetric phantoms with smooth, well-

Journal of the American Society of Echocardiography Volume I1 Number 12

d e f i n e d , o p t i m a l l y d e l i n e a t e d b o r d e r s . We d i d n o t include rubber balloons with distorted shape b e c a u s e m o d e l s t h a t aUow s i m u l t a n e o u s c o n t r a c t i o n a n d e x p a n s i o n o f d i f f e r e n t s e g m e n t s at t h e s a m e t i m e w e r e n o t available. H o w e v e r , o n t h e basis o f t h e e x p e r i e n c e o f o u r p r e v i o u s in vitro study, 21 w e do not believe that this would have significantly c h a n g e d o u r results.To r e d u c e t h e m o t i o n artifacts o f t h e p h a n t o m s in t h e w a t e r b a t h d u r i n g t h e dynamic e x p e r i m e n t , w e u s e d a s i n u s o i d a l c o n t r a c t i o n patt e r n instead o f t h e t r u e p h y s i o l o g i c p a t t e r n of contraction. T h e r e f o r e , t h e d u r a t i o n o f b o t h systole and diastole w e r e equally affected by s h o r t e n i n g o f t h e cardiac cycle w i t h i n c r e a s i n g h e a r t l a t e in contrast to p r e d o m i n a n t diastolic s h o r t e n i n g in n o r m a l physiology. T h i s m a y h a v e r e s u l t e d in a n i n c r e a s e d meas u r e m e n t variability o f b o t h EDV and ESV magnifying t h e h e a r t r a t e - d e p e n d e n t m e a s u r e m e n t e r r o r o f EF calculation. A n o t h e r limitation is tile p r e d e f i n e d slice t h i c k n e s s o f 1 m m a n d 5 r a m , r e s p e c t i v e l y . O t h e r investigators h a v e r e c e n t l y s h o w n t h a t a slice t h i c k n e s s o f u p to 15 ~ can b e u s e d for t h e assessm e n t o f EF by u s i n g 3DE w i t h o u t losing accuracy. 20 T h i s w o u l d certainly result in a significant r e d u c t i o n o f tracing w o r k a n d t i m e r e q u i r e m e n t s for analysis. I n V i v o S t u d i e s . A w e l l - k n o w n limitation for t h e c o m p a r i s o n to a n g i o g r a p h y is t h a t b o t h studies w e r e n o t p e r f o r m e d s i m u l t a n e o u s l y We are a w a r e t h a t t h e lintited n m n b e r of p a t i e n t s w i t h s y m m e t r i c left ventricles i n c l u d e d in t h e study m a y h a v e led to signific a n t bias. It is a c l e a r l i m i t a t i o n o f t h e s t u d y t h a t t h e r e is no g o l d s t a n d a r d for in v i v o v o l u m e measurements. M a g n e t i c r e s o n a n c e i m a g i n g w o u l d have b e e n t h e p r e f e r r e d m e t h o d for c o m p a r i s o n b e c a u s e it has an e x c e l l e n t spatial r e s o l u t i o n and d o e s n o t n e e d g e o m e t r i c a s s u m p t i o n s similar to 3DE. 4~ Yet, this m e t h o d w a s n o t available in t h e c u r r e n t study. O n e of t h e major d r a w b a c k s o f t h e c o n t i n u o u s CO system is its insensitivity to a c u t e c h a n g e s o f CO. 41 Therefore, t h e r e may have b e e n significant c h a n g e s in CO d u r i n g t h e e c h o c a r d i o g r a p h i c data acquisition t h a t w e r e n o t d e t e c t e d by t h e t h e r m o d l l u t i o n syst e m . A n o t h e r limitation is the lack o f a t r u e g o l d standard. Because t h e t r u e values o f C O are u n k n o w n , a p r e c i s e in vivo validation o f a n e w m e t h o d is impossible against a n i n a c c u r a t e standard. T h u s 3DE may be even more accurate than thermodllution.

CONCLUSIONS T h r e e - d i m e n s i o n a l e c h o c a r d i o g r a p h y w i t h multip l a n e TEE allows a c c u r a t e d e t e r m i n a t i o n o f LV volu m e s and EE as d e m o n s t r a t e d in a dynamic in vitro

K/ihl et al 1 1 2 3

study. H o w e v e r , t h e a c c u r a c y o f EF c a l c u l a t i o n d e c r e a s e s w i t h i n c r e a s i n g h e a r t rate. C o m p a r e d w i t h b i p l a n e a n g i o g r a p h y , 3DE w i t h m u l t i p l a n e TEE s h o w e d h i g h a g r e e m e n t in p a t i e n t s w i t h s y m m e t r i c LV g e o m e t r y . C o r r e l a t i o n b e t w e e n t h e 2 m e t h o d s w a s also g o o d for c a l c u l a t i o n o f LV v o l u m e s in p a t i e n t s w i t h d i s t o r t e d ventricles, b u t t h e r e w a s less a g r e e m e n t . T h i s m e t h o d allows d e t e r m i n a t i o n o f CO and SV in critically ill, v e n t i l a t e d patients, a l t h o u g h there was a systematic underestimation compared with the continuous thermodllntion method.

REFERENCES

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Journal of the American Society of Echocardiography December 1998

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