- Email: [email protected]
Accuracy of mitral Doppler echocardiographic cardiac output determinations in adults
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Accuracy of mitral Doppler echocardiographic cardiac output determinations in adults The Doppler echocardiographic estimation of cardiac output at the mitral valve site is often underestimated in adults with slow heart rates because the mitral valve remains open in mid-diastole when flow is markedly reduced. Therefore we tested several approaches to this measurement in 17 adults with nonvalvular heart disease who had thermodilution catheters in the right side of the heart. Superior correlations with thermal output values were obtained by a new method that excludes mitral orifice measurements during mid-diastole when flow < 10 c m / s e c (r = 0.94) c o m p a r e d with the standard method (r = 0.89). Also, the new method resulted in significantly less underestimation of thermal cardiac output in patients with heart rates < 70 beats/rain ( - 1 0 % ) compared with the standard method (-34%). In addition, use of a constant maximal two-dimensional echocardiographic mitral orifice correction factor of 0.77 with the new method to account for variations in mitral valve orifice during the cardiac cycle, as opposed to 0.68 with the standard method, resulted in similar results as compared with determining individual correction factors from M-mode echoes. We conclude that: (1) the mitral orifice approach is accurate for measuring cardiac output in adult patients with nonvalvular heart disease; (2) a new method that excludes mid-diastolic mitral orifice measurements is superior to the standard method; and (3) use of a constant two-dimensional echocardiographic mitral valve orifice correction factor obviates the need for M-mode echoes. (AM HEART J 1990;119:905.)
William E. Miller, MD, Kent L. Richards, MD, and Michael H. Crawford, MD.
San Antonio, Texas
Cardiac output can be measured noninvasively by determining mean cross-sectional area from imaging echocardiography, the velocity-time integral from Doppler echocardiography, and the heart rate. Determination of cardiac output from multiple sites allows calculation of regurgitant or shunt flow rates, permits the estimation of stenotic valve areas by measuring flow at an alternate site, and provides confirmation of data by measuring the same flow rates at more than 1 site. Techniques have been developed in animal flow models and in pediatric patients for calculating flow at all four cardiac valves. 1-5 In adults, aortic and mitral sites are most commonly utilized because pulmonic and tricuspid valve cross-sectional areas are difficult to determine accurately by imaging echocardiography. While the clinical usefulness of the aortic site has been well documented in adults, utilization of the From the University of Texas Health Science Center and Veterans Administration Hospital. Supported in part by the Veterans Administration Hospital. Received for publication July 24, 1989: accepted Dec. 1, t989. Reprint requests: Michael H. Crawford. MD. Dept. of Medicine/Cardiology, University of New Mexico School of Medicine, Albuquerque, NM 87131. 4/1/18618
mitral valve orifice has been more difficult because of the marked changes in valvular cross-sectional area that occur during diastole. Fisher et al. 6 developed a method of estimating mean mitral cross-sectional area using M-mode echocardiographically determined mean mitral leaflet separation to adjust maximum diastolic orifice size measured from the twodimensional echocardiograms. Although it proved accurate in the animal model and in a pediatric population, less reliable results were observed when this method was attempted in an adult population. 7 In a pilot study, we noted significant underestimation of cardiac output when the method of Fisher et al. was used in adults with heart rates < 70 beats/rain. Therefore the purposes of our study were: (1) to further define the accuracy the method of Fisher et al. in calculating cardiac output in a population of adults with heart disease; (2) to assess the reasons for increased inaccuracy of their method in the presence of low heart rates; and (3) to test the performance of three additional methods using the mitral orifice site. METHODS P a t i e n t information. Twenty patients admitted to the
coronary care unit for monitoring of cardiac output with thermodilution right-sided heart catheters participated in 905
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AmericanHeartJournal
Fig. 1. Left, M-mode echocardiogram of mitral valve (top) showing maximum diastolic opening between the anterior and posterior leaflets (Dmax), the diastolic distance-time area between the leaflets (DT), and the diastolic filling time (T). Mitral Doppler spectral recording (bottom) shows the velocity-time integral (VT). Middle, Same measures in a patient with bradycardia. Right, Same patient as in middle panel showing early diastolic leaflet separation distance-time area (DT1) and the late diastolic distance-time area (DT2), the corresponding diastolic filling times (TI and T2), and velocity-time integrals (VT1 and VT2). See text for details.
the study. All were in normal sinus rhythm; none had echocardiographic evidence of mitral valve disease. Highquality echocardiographic data were obtained in 17 (85 To). In the study population, age ranged from 53 to 69 (mean = 62) years. Fifteen had angina pectoris and five had clinical evidence of congestive heart failure. Thermodiiution cardiac output. Thermodilution cardiac output was performed with a 7F Swan-Ganz catheter (VIP catheter, Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.) and a bedside cardiac output computer (Series 7000, Marquette Electronics Inc., Milwaukee, Wisc.). Thermodilution cardiac output measurements were performed immediately following echocardiographic examination by injecting 10 cm 3 of iced saline. The average of three determinations was used as the standard of reference. Echocardiographic examination. All echocardiographic examinations were performed with a 2.25 MHz duplex pulsed Doppler ultrasonoscope (Ultramark-8, Advanced Technology Laboratories, Inc., Bothell, Wash.). Two-dimensional images were stored on VHS videotape. M-mode and Doppler echocardiographic records were made with a 6-inch paper chart recorder (LS-8, Honeywell Test Instruments, Denver, Colo.) at a paper speed of 100 mm/sec. Quantitative measurements were made on an off-line analysis system (Microsonics, Indianapolis, Ind., Software version 2.5). Maximum mitral orifice cross-sectional area was recorded at the tips of the mitral valve leaflets using a parasternal short-axis view. Care was taken to measure the largest diastolic cross-sectional area with well-defined anterior and posterior mitral valve leaflets. The M-mode image was obtained by placing the M-mode cursor through
the largest anterior-posterior diameter of the same two-dimensional short-axis image of the mitral orifice. Doppler spectral recordings were obtained with duplex pulsed Doppler with a 5 mm axial sample volume length. An apical four-chamber view was utilized to position the sample volume between the anterior and posterior leaflets within or immediately downstream from the mitral valve orifice. Slight transducer and sample volume position changes were required to obtain the highest Doppler frequency shift; velocities were calculated with an assumed Doppler angle of 0 degrees. Wall filters were adjusted from 100 to 200 Hz to suppress cardiac motion and valve leaflet artifacts. Equations for calculation of cardiac output at the mitral orifice. Clinically useful estimates of cardiac output
(CO) can be calculated as the product of mean crosssectional area (Amean), velocity-time integral (VT), and heart rate (HR): CO = (Amean) (VT) (HR). Because mitral cross-sectional area changes markedly during diastole, a correction factor (CF) is required to estimate mean from maximal (Amax) cross-sectional area: (Amean)= (CF) (Amax). Four different correction factors were investigated. The first, which was proposed by Fisher et al., 6 used the ratio of mean (Dmean) and maximal (Dmax) distance separating the anterior and posterior mitral valve leaflets during diastole. As shown in Fig. 1, Dmean was calculated as the distance-time area (DT) between the anterior and posterior leaflets divided by the time of diastolic separation (T). M-mode records were analyzed from each patient to determine correction factor 1 (CF-1): CF-1 = (DT/T)/(Dmax). To simplify the calculation of output, the average mitral valve CF of Fisher et al. for the entire study population was
Volume 119
Cardiac output by mitral Doppler-echo
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Table I. Individual p a t i e n t d a t a
Cardiac output Correction factor
Doppler echo
Heart rate (beats~rain)
M-mode 1
Mitral valve 3
MVAmax (cm2)
VT (cm/beat)
53 53 53 55 59 62 67 68 75 75 76 81 84 93 97 97 123 Mean 75
0.55 0.47 0.50 0.59 0.51 0.59 0.95 0.54 0.81 0.61 0.86 0.77 0.72 0.71 0.80 0.78 0.72 0.68
0.80 0.78 0.75 0.70 0.70 0.85 0.95 0.79 0.81 0.67 0.86 0.77 0.72 0.71 0.81 0.78 0.72 0.77
6.1 6.1 4.8 5.4 6.1 5.6 4.8 6.2 9.1 5.8 4.4 5.9 7.1 4.3 6.4 5.8 3.3 5.7
18.6 18.7 21.3 19.2 24.9 15.3 16.7 14.9 9.1 11.6 23.9 18.0 16.2 11.5 11.3 12.9 8.5 16.0
1
2
3
4
Cath TD
3.3 2.8 2.7 3.4
4.1 4.1 3.7 3.9 6.1 3.6 3.7 4.3 2.6 3.4 5.4 5.8 6.6 3.1 4.8 4.9 2.3 4.3
4.8 4.7 4.1 4.0 6.3 4.5 5.1 5.0 3.2 3.4 6.9 6.6 7.0 3.3 5.6 5.7 2.5 4.9
4.6 4.6 4.2 4.4 6.9 4.1 4,2 4.9 2.9 3.9 6.1 6.6 7.5 3.5 5.4 5.5 2.6 4.9
5.0 5.1 4.4 5,0 6.2 5.6 5.6 5.6 4,3 4.6 7.3 6.9 8,7 3.6 6.6 6,8 2.8 5,5
3.1 5.1 3.4 3.2 3.1 6.9 6.6 7.0 3.3 5.6 5.7 2.5 4.3
MVAmax, Maximal mitral valve orifice area by two-dimensional echocardiography; VT, velocity-time integral by Doppler; Cath, catheterization; TD, thermodilution cardiac output.
determined and was used to correct each individual maximal mitral valve cross-sectional area. Correction factor 3 (CF-3) excluded the period of diastasis in the calculation of mean mitral leaflet separation. As diastolic velocities were low or 0 in mid-diastole, the average leaflet separation was calculated in early (DT1/T1) and late (DT2/T2) diastole. T h e period of diastasis on the M - m o d e image was defined from cycle length-matched Doppler spectral tracings (see below). These two average leaflet separations were utilized to approximate mean leaflet separation: CF-3 = [(DT1/T1) + (DT2/T2)] / [Dmax]. CF 4 is the average of CF-3 for the entire study population and was used to correct individual maximum mitral valve cross-sectional areas. Echocardiographic measurements. All M-mode, twodimensional, and Doppler echocardiographic d a t a were analyzed by an investigator who was unaware of the thermodilution cardiac o u t p u t results. The average of three beats was used for all echocardiographic cardiac o u t p u t calculations. Fig. i shows M-mode echocardiograms in the top panels and Doppler spectral tracings in the bottom panels from patients with normal (left) and slow (middle and right) heart rates. The M - m o d e and Doppler tracings have been aligned to illustrate the t e m p o r a l sequence of mitral velocity and leaflet separation; note t h a t bradycardia can result in moderate separation of the mitral leaflets at a time when velocity across the valve is very low. T h e modal velocity was utilized to measure the diastolic mitral velocity-time integral (VT) from Doppler spectral recordings. The M - m o d e
image was used to calculate Dmax, DT, and T. As shown in the patient with bradycardia in the right panel, early and late diastolic velocity-time integrals (VT1 and VT2, respectively) and DT1/T1 and D T 2 / T 2 were calculated using the time of "0" velocity as the indicator for termination and resumption of mid-diastolic flow. Statistical analysis. Correlations between thermodilution and echocardiographic c a r d i a c o u t p u t measurements were tested by linear regression using a least squares analysis. Confidence limits of 95% were utilized. Comparison of the percent difference between thermodilution and echocardiographic cardiac o u t p u t by each method was performed for patients w i t h h e a r t rates <70 beats/rain and also for patients with heart rates >70 beats/min using Stud e n t ' s t test. Significance was defined as p < 0.05. RESULTS
A s u m m a r y o f p e r t i n e n t echocardiographic m e a surements and cardiac output determinations by thermodilution and by each Doppler echocardiographic method are displayed for each study patient i n T a b l e I. P a t i e n t s a r e l i s t e d in o r d e r f r o m t h e lowe s t (53 b e a t s / r a i n ) t o t h e h i g h e s t (123 b e a t s / r a i n ) h e a r t r a t e . E i g h t o f 17 a d u l t s h a d h e a r t r a t e s < 7 0 b e a t s / r a i n . M e a n v a l u e s for e a c h p a r a m e t e r a r e shown at the bottom under each column of data. Cardiac output determinations by the thermodilut i o n t e c h n i q u e w e r e 2.8 t o 8.7 ( m e a n = 5.5) L / r a i n . A l l
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diac output (COzcho-S through4)
versus
thermal dilution cardiac output (COTD). See text for details.
echocardiographic techniques underestimated thermodilution cardiac output; underestimation was less when Methods No. 3 or 4 were utilized. Fig. 2 shows the results of cardiac output by thermodilution on the X axes versus cardiac output by echocardiographic Methods No. 1 to 4 (see below) on the Y axes. There was a good correlation between thermodilution and echocardiographic cardiac output determinations predicted by the method of Fisher et al. (Echo-l: r = 0.89; SEE = 0.75 L/min). To simplify the calculation, the average CF was used as a constant to calculate cardiac output from the same heart rate, maximum orifice area, and velocitytime integral (Echo-2). The right upper panel of Fig. 2 shows a good correlation between thermodilution cardiac output and that predicted using the average Fisher et al. correction factor (Echo-2: r---0.91; SEE = 0.51 L/rain). Although the correlation coefficients for echocardiographic methods No. 1 and 2 are similar, the standard error of the estimate was markedly smaller when the average correction factor was utilized. The left lower panel of Fig. 2 shows a good correlation between thermodilution and Echo-3 cardiac output data, in which individual early and late diastolic M-mode data were utilized (Echo-3: r --- 0.94; SEE = 0.46 L/min). As shown in the right lower panel of Fig. 2, there was a good correlation between thermodilution and Doppler echocardiographic cardiac output determinations calculated using the average early and late diastolic M-mode data (Echo-4: r = 0.91; SEE = 0.58 L/min). As shown by the bar graph in Fig. 3, Echo-1 underestimated cardiac output by an average of 34 % in the eight patients with heart rates <70 beats/min and by
an average of 15% in the nine patients with heart rates >70 beats/min. Echo-2 underestimated output by 21% in adults with slow heart rates and by 23 % in those with heart rates >70 beats/min. The differences between Echo-1 and Echo-2 in both groups of patients were statistically significant. Echo-3 underestimated thermodilution cardiac output by an average of 10 To and 15 % for patients with heart rates that were <70 and >70 beats/min, respectively. This represented a statistically significant reduction in underestimation of output compared with Echo-1 and Echo-2 methods at heart rates <70 beats/rain and to Echo-2 at heart rates >70 beats/min. There were no significant differences in mean cardiac output determinations between patients with heart rates <70 or >70 beats/min when Echo-3 and Echo-4 were compared. DISCUSSION
In the course of assessing the method of Fisher et al. in adults, we found that cardiac output was markedly underestimated at heart rates <70 beats/rain. Their approach assumes that mean velocity and cross-sectional area can be used to quantify mitral valve cardiac output. Accurate quantification of stroke volume at the mitral valve orifice must consider that both velocity and cross-sectional area are pulsatile and thus change continuously throughout diastole. Stroke volume is the sum of all the instantaneous velocity-time integral (VTi) and cross-sectional area (Ai) products measured during diastole: SV = E (VTi) (Ai). The Fisher equation, which: uses a single diastolic velocity-t/me integral and mean cross-sectional area, fails to account for conditions in
V o l u m e 119
Cardiac output by rnitral Doppler-echo
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Fig. 3. Percent difference between the four echocardiographic methods and thermal dilution cardiac output determinations in patients with heart rate (HR) <70 beats/min and >70 beats/min. See text for details.
mid-diastole when cross-sectional area may remain large despite minimal blood flow across the mitral valve. Data from a patient whose heart rate was <70 beats/min are shown in the middle and right panels of Fig. 1. It is important to note that the mitral valve orifice remains open in mid-diastole despite the fact that there is little or no flow across the valve. Because the method of Fisher et al. determines average crosssectional area of the valve orifice during all of diastole and not just when there is flow across the valve, it underestimates cross-sectional area present during early and late diastole when velocities are highest. Thus any mitral valve method that does not utilize instantaneous cross-sectional area times instantaneous velocity products will theoretically underestimate true mitral valve flow rate. This will be most marked if the heart rate is slow enough to allow flow to approach 0 in middle diastole when the mitral leaflets remain open. Such conditions are theoretically present at both the mitral valve orifice and the mitral anulus and should lead to inaccuracy at both sites in patients with slower heart rates. In our eight patients with heart rates <70 beats/ min, Doppler tracings documented a mid-diastolic period of mitral valve velocities of <10 cm/sec. During this time the mitral anterior and posterior leaflets remained partially opened in all patients. Similar diastasis has been documented in animal preparations in which an electromagnetic flow meter confirmed 0 flow at a time when mitral leaflets were partially opened, s Recently, Binkley et al. 9 confirmed these observations in adults with bradydysrhythmias using combined Doppler and imaging echocardiography. Although the heart rates in the study of Fisher et al. are not stated, it can be assumed that they were
>70 beats/min because the experiments involved dogs and children. Stewart et al. 1~confirmed the accuracy of Fisher's method in a similar canine model and calculated an average M-mode correction factor of 0.68, identical to the one we measured using the Fisher technique. In their experiments, results with the average correction factor did not differ from those derived using individual correction factors, and they concluded that M-mode echocardiography was not necessary, Two other simplifications of the method of Fisher et al. have been proposed. Lewis et al. 11 used maximum mitral anulus area in diastole and flow velocity integral at the same site, which was found to be accurate when compared with thermodilution determinations in hospitalized patients. Meijboom et al. 12 studied a similar method in a dog model and in children. This technique used mitral anulus area calculated from two-dimensional echocardiograhic annular diameters in the apical views as did Lewis et al., but flow velocity integral was measured distal to the mitral leaflet tips in the left ventricular inflow area. Their method correlated well with the method of Fisher et al. in the dog model and with thermodilution cardiac output determinations in the children. Although the above studies suggest that M-mode echocardiography is not necessary for the accurate estimation of cardiac output at the mitral area, none of them addressed the issue of heart rate effects on the measurements. H e a r t rate probably is not the only source of error in the mitral Doppler cardiac output estimations. Measuring mitral valve orifice area by two-dimensional ech0cardiography is challenging in many adults. Interestingly, the mitral anulus method of Lewis et al. 11 resulted in less underestimation of cardiac output despite the fact that mitral orifice area
910
Miller, Richards, and Crawford
was a s s u m e d to be c o n s t a n t t h r o u g h o u t diastole. Alt h o u g h h e a r t rate d a t a were n o t provided in this study, p e r h a p s other errors offset the p r o b l e m of using a fixed orifice during the period of low flow in mid-diastole. Lateral resolution problems at the great d e p t h of the anulus in apical views or errors due to assuming a circular shape of the anulus m a y have i n t r o d u c e d offsetting errors. Also, velocity is generally lower at the anulus as Compared with the leaflet tips, as Lewis et al. 11 noted. Since accurate velocity m e a s u r e m e n t s d e p e n d on the angle of the Doppler b e a m to the flow stream, a n y error i n t r o d u c e d by assuming a zero angle m a y be increased in areas of low velocity. U n d e r e s t i m a t i o n of velocity in early and late diastole m a y increase average flow calculations from an a s s u m e d fixed orifice. Only a s t u d y using multiple i n s t a n t a n e o u s velocity and orifice area meas u r e m e n t t h r o u g h o u t diastole comparing the various m e t h o d s would answer these questions. In conclusion, our investigation supports the usefulness of the m e t h o d of Fisher et al. in estimating cardiac o u t p u t using the mitral valve orifice site in adults, and confirms t h a t M - m o d e echocardiographic images of the mitral orifice are n o t required to calculate cardiac output. However, it identifies patients with h e a r t rates of <70 b e a t s / m i n as individuals in w h o m cardiac o u t p u t can be significantly underestim a t e d if the mid-diastolic cross-sectional area of the mitral orifice is included in the correction factor used to estimate m e a n mitral cross-sectional area from the m a x i m u m area. T h u s a c o n s t a n t of 0.77 (not 0.68) should be used to estimate m e a n from m a x i m u m mitral orifice cross-sectional area in adults, because it considers the often slow h e a r t rates e n c o u n t e r e d in adults with cardiac disease. REFERENCES
1. AlversonDC, Eldridge M, Dillion T, Yabek SM, Berman W Jr. Noninvasive pulsed Doppler determination of cardiac output in neonates and children. J Pediatr 1982;101:46-50.
April 1990 American Heart Journal
2. Fisher DC, Sahn DJ, Friedman MJ, Larson D, Valdes-Cruz LM, Horowitz S, Goldberg SJ, Allen HD. The effect of variations on pulsed Doppler sampling site on calculation of cardiac output: an experimental study in open-chest dogs. Circulation 1983;67:370-6. 3. Goldberg SJ, Sahn DJ, Allen H, Valdes-Cruz LM. Evaluation of pulmonary and systemic blood flow by two-dimensional echo Doppler using fast Fourier transform spectral analysis. Am J Cardiol 1982;50:1394-400. 4. Huntsman LL, Stewart DK, Barnes SR, Franklin SB, Coloeousis JS, Hessel EA. Noninvasive Doppler determination of cardiac output in man. Clinical validation. Circulation 1983;67:593-602. 5. MeijboomEJ, Horowitz S, Valdes-Cruz LM, Sahn DJ, Larson DF, Olivera Lima C. A Doppler echocardiographicmethod for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies. Circulation 1985;71:551-6. 6. Fisher DC, Sahn DJ, Friedman MJ, Larson D, Valdes-Cruz LM, Horowitz S, Goldberg SJ, Allen HD. The mitral valve orifice method for noninvasive two-dimensional echo Doppler determinations of Cardiac output. Circulation 1983;67:872-7. 7. Loeber CP, Goldberg SJ, Allen HD. Doppler echocardiographic comparison of flows distal to the four cardiac views. J Am Co]l Cardiol 1984;4:268-72. 8. Meisner JS, McQueen DM, Ishida Y, Vetter HO, Bortolotti U, Strom JA, Frater RWM, Peskin CS, Yellin EL. Effects of timing of atrial systole on LV filling and mitral valve closure: computer and dog studies. Am J Physiol 1985;249:H604-19. 9. Binkley PF, Bonagura JD, Olson SM, Boudoulas H, Wooley CF. The equilibrium position of the mitral valve: an accurate model of mitral valve motion in humans. Am J Cardiol 1987;59:109-13. 10. Stewart WJ, Leng J, Mich R, Pandian N, Guerrero JL, Weyman AE. Variable effects of changes in flow rate through the aortic, pulmonary and mitral valves on valve area and flowvelocity: impact on quantitative Doppler flowcalculations. J Am Coll Cardiol 1985;6:653-62. 11. Lewis JF, Kuo LC, Nelson JC, Limacher MC, Quinones MA. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation 1984;70:425-31. 12. MeijboomEJ, Horowitz S, Valdes-Cruz LM, Larson DF, Born N, Rijsterborgh H, Olivera Lima C, Sahn DJ. A simplified mitral valve method for two-dimensional echo Doppler blood flowcalculation:Validation in an open-chest canine model and initial clinical studies. AM HEARTJ 1987;113:335-40.
III
I
I
Accuracy of mitral Doppler echocardiographic cardiac output determinations in adults The Doppler echocardiographic estimation of cardiac output at the mitral valve site is often underestimated in adults with slow heart rates because the mitral valve remains open in mid-diastole when flow is markedly reduced. Therefore we tested several approaches to this measurement in 17 adults with nonvalvular heart disease who had thermodilution catheters in the right side of the heart. Superior correlations with thermal output values were obtained by a new method that excludes mitral orifice measurements during mid-diastole when flow < 10 c m / s e c (r = 0.94) c o m p a r e d with the standard method (r = 0.89). Also, the new method resulted in significantly less underestimation of thermal cardiac output in patients with heart rates < 70 beats/rain ( - 1 0 % ) compared with the standard method (-34%). In addition, use of a constant maximal two-dimensional echocardiographic mitral orifice correction factor of 0.77 with the new method to account for variations in mitral valve orifice during the cardiac cycle, as opposed to 0.68 with the standard method, resulted in similar results as compared with determining individual correction factors from M-mode echoes. We conclude that: (1) the mitral orifice approach is accurate for measuring cardiac output in adult patients with nonvalvular heart disease; (2) a new method that excludes mid-diastolic mitral orifice measurements is superior to the standard method; and (3) use of a constant two-dimensional echocardiographic mitral valve orifice correction factor obviates the need for M-mode echoes. (AM HEART J 1990;119:905.)
William E. Miller, MD, Kent L. Richards, MD, and Michael H. Crawford, MD.
San Antonio, Texas
Cardiac output can be measured noninvasively by determining mean cross-sectional area from imaging echocardiography, the velocity-time integral from Doppler echocardiography, and the heart rate. Determination of cardiac output from multiple sites allows calculation of regurgitant or shunt flow rates, permits the estimation of stenotic valve areas by measuring flow at an alternate site, and provides confirmation of data by measuring the same flow rates at more than 1 site. Techniques have been developed in animal flow models and in pediatric patients for calculating flow at all four cardiac valves. 1-5 In adults, aortic and mitral sites are most commonly utilized because pulmonic and tricuspid valve cross-sectional areas are difficult to determine accurately by imaging echocardiography. While the clinical usefulness of the aortic site has been well documented in adults, utilization of the From the University of Texas Health Science Center and Veterans Administration Hospital. Supported in part by the Veterans Administration Hospital. Received for publication July 24, 1989: accepted Dec. 1, t989. Reprint requests: Michael H. Crawford. MD. Dept. of Medicine/Cardiology, University of New Mexico School of Medicine, Albuquerque, NM 87131. 4/1/18618
mitral valve orifice has been more difficult because of the marked changes in valvular cross-sectional area that occur during diastole. Fisher et al. 6 developed a method of estimating mean mitral cross-sectional area using M-mode echocardiographically determined mean mitral leaflet separation to adjust maximum diastolic orifice size measured from the twodimensional echocardiograms. Although it proved accurate in the animal model and in a pediatric population, less reliable results were observed when this method was attempted in an adult population. 7 In a pilot study, we noted significant underestimation of cardiac output when the method of Fisher et al. was used in adults with heart rates < 70 beats/rain. Therefore the purposes of our study were: (1) to further define the accuracy the method of Fisher et al. in calculating cardiac output in a population of adults with heart disease; (2) to assess the reasons for increased inaccuracy of their method in the presence of low heart rates; and (3) to test the performance of three additional methods using the mitral orifice site. METHODS P a t i e n t information. Twenty patients admitted to the
coronary care unit for monitoring of cardiac output with thermodilution right-sided heart catheters participated in 905
April 1990
906
Miller, Richards, and Crawford
AmericanHeartJournal
Fig. 1. Left, M-mode echocardiogram of mitral valve (top) showing maximum diastolic opening between the anterior and posterior leaflets (Dmax), the diastolic distance-time area between the leaflets (DT), and the diastolic filling time (T). Mitral Doppler spectral recording (bottom) shows the velocity-time integral (VT). Middle, Same measures in a patient with bradycardia. Right, Same patient as in middle panel showing early diastolic leaflet separation distance-time area (DT1) and the late diastolic distance-time area (DT2), the corresponding diastolic filling times (TI and T2), and velocity-time integrals (VT1 and VT2). See text for details.
the study. All were in normal sinus rhythm; none had echocardiographic evidence of mitral valve disease. Highquality echocardiographic data were obtained in 17 (85 To). In the study population, age ranged from 53 to 69 (mean = 62) years. Fifteen had angina pectoris and five had clinical evidence of congestive heart failure. Thermodiiution cardiac output. Thermodilution cardiac output was performed with a 7F Swan-Ganz catheter (VIP catheter, Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.) and a bedside cardiac output computer (Series 7000, Marquette Electronics Inc., Milwaukee, Wisc.). Thermodilution cardiac output measurements were performed immediately following echocardiographic examination by injecting 10 cm 3 of iced saline. The average of three determinations was used as the standard of reference. Echocardiographic examination. All echocardiographic examinations were performed with a 2.25 MHz duplex pulsed Doppler ultrasonoscope (Ultramark-8, Advanced Technology Laboratories, Inc., Bothell, Wash.). Two-dimensional images were stored on VHS videotape. M-mode and Doppler echocardiographic records were made with a 6-inch paper chart recorder (LS-8, Honeywell Test Instruments, Denver, Colo.) at a paper speed of 100 mm/sec. Quantitative measurements were made on an off-line analysis system (Microsonics, Indianapolis, Ind., Software version 2.5). Maximum mitral orifice cross-sectional area was recorded at the tips of the mitral valve leaflets using a parasternal short-axis view. Care was taken to measure the largest diastolic cross-sectional area with well-defined anterior and posterior mitral valve leaflets. The M-mode image was obtained by placing the M-mode cursor through
the largest anterior-posterior diameter of the same two-dimensional short-axis image of the mitral orifice. Doppler spectral recordings were obtained with duplex pulsed Doppler with a 5 mm axial sample volume length. An apical four-chamber view was utilized to position the sample volume between the anterior and posterior leaflets within or immediately downstream from the mitral valve orifice. Slight transducer and sample volume position changes were required to obtain the highest Doppler frequency shift; velocities were calculated with an assumed Doppler angle of 0 degrees. Wall filters were adjusted from 100 to 200 Hz to suppress cardiac motion and valve leaflet artifacts. Equations for calculation of cardiac output at the mitral orifice. Clinically useful estimates of cardiac output
(CO) can be calculated as the product of mean crosssectional area (Amean), velocity-time integral (VT), and heart rate (HR): CO = (Amean) (VT) (HR). Because mitral cross-sectional area changes markedly during diastole, a correction factor (CF) is required to estimate mean from maximal (Amax) cross-sectional area: (Amean)= (CF) (Amax). Four different correction factors were investigated. The first, which was proposed by Fisher et al., 6 used the ratio of mean (Dmean) and maximal (Dmax) distance separating the anterior and posterior mitral valve leaflets during diastole. As shown in Fig. 1, Dmean was calculated as the distance-time area (DT) between the anterior and posterior leaflets divided by the time of diastolic separation (T). M-mode records were analyzed from each patient to determine correction factor 1 (CF-1): CF-1 = (DT/T)/(Dmax). To simplify the calculation of output, the average mitral valve CF of Fisher et al. for the entire study population was
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Cardiac output by mitral Doppler-echo
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Table I. Individual p a t i e n t d a t a
Cardiac output Correction factor
Doppler echo
Heart rate (beats~rain)
M-mode 1
Mitral valve 3
MVAmax (cm2)
VT (cm/beat)
53 53 53 55 59 62 67 68 75 75 76 81 84 93 97 97 123 Mean 75
0.55 0.47 0.50 0.59 0.51 0.59 0.95 0.54 0.81 0.61 0.86 0.77 0.72 0.71 0.80 0.78 0.72 0.68
0.80 0.78 0.75 0.70 0.70 0.85 0.95 0.79 0.81 0.67 0.86 0.77 0.72 0.71 0.81 0.78 0.72 0.77
6.1 6.1 4.8 5.4 6.1 5.6 4.8 6.2 9.1 5.8 4.4 5.9 7.1 4.3 6.4 5.8 3.3 5.7
18.6 18.7 21.3 19.2 24.9 15.3 16.7 14.9 9.1 11.6 23.9 18.0 16.2 11.5 11.3 12.9 8.5 16.0
1
2
3
4
Cath TD
3.3 2.8 2.7 3.4
4.1 4.1 3.7 3.9 6.1 3.6 3.7 4.3 2.6 3.4 5.4 5.8 6.6 3.1 4.8 4.9 2.3 4.3
4.8 4.7 4.1 4.0 6.3 4.5 5.1 5.0 3.2 3.4 6.9 6.6 7.0 3.3 5.6 5.7 2.5 4.9
4.6 4.6 4.2 4.4 6.9 4.1 4,2 4.9 2.9 3.9 6.1 6.6 7.5 3.5 5.4 5.5 2.6 4.9
5.0 5.1 4.4 5,0 6.2 5.6 5.6 5.6 4,3 4.6 7.3 6.9 8,7 3.6 6.6 6,8 2.8 5,5
3.1 5.1 3.4 3.2 3.1 6.9 6.6 7.0 3.3 5.6 5.7 2.5 4.3
MVAmax, Maximal mitral valve orifice area by two-dimensional echocardiography; VT, velocity-time integral by Doppler; Cath, catheterization; TD, thermodilution cardiac output.
determined and was used to correct each individual maximal mitral valve cross-sectional area. Correction factor 3 (CF-3) excluded the period of diastasis in the calculation of mean mitral leaflet separation. As diastolic velocities were low or 0 in mid-diastole, the average leaflet separation was calculated in early (DT1/T1) and late (DT2/T2) diastole. T h e period of diastasis on the M - m o d e image was defined from cycle length-matched Doppler spectral tracings (see below). These two average leaflet separations were utilized to approximate mean leaflet separation: CF-3 = [(DT1/T1) + (DT2/T2)] / [Dmax]. CF 4 is the average of CF-3 for the entire study population and was used to correct individual maximum mitral valve cross-sectional areas. Echocardiographic measurements. All M-mode, twodimensional, and Doppler echocardiographic d a t a were analyzed by an investigator who was unaware of the thermodilution cardiac o u t p u t results. The average of three beats was used for all echocardiographic cardiac o u t p u t calculations. Fig. i shows M-mode echocardiograms in the top panels and Doppler spectral tracings in the bottom panels from patients with normal (left) and slow (middle and right) heart rates. The M - m o d e and Doppler tracings have been aligned to illustrate the t e m p o r a l sequence of mitral velocity and leaflet separation; note t h a t bradycardia can result in moderate separation of the mitral leaflets at a time when velocity across the valve is very low. T h e modal velocity was utilized to measure the diastolic mitral velocity-time integral (VT) from Doppler spectral recordings. The M - m o d e
image was used to calculate Dmax, DT, and T. As shown in the patient with bradycardia in the right panel, early and late diastolic velocity-time integrals (VT1 and VT2, respectively) and DT1/T1 and D T 2 / T 2 were calculated using the time of "0" velocity as the indicator for termination and resumption of mid-diastolic flow. Statistical analysis. Correlations between thermodilution and echocardiographic c a r d i a c o u t p u t measurements were tested by linear regression using a least squares analysis. Confidence limits of 95% were utilized. Comparison of the percent difference between thermodilution and echocardiographic cardiac o u t p u t by each method was performed for patients w i t h h e a r t rates <70 beats/rain and also for patients with heart rates >70 beats/min using Stud e n t ' s t test. Significance was defined as p < 0.05. RESULTS
A s u m m a r y o f p e r t i n e n t echocardiographic m e a surements and cardiac output determinations by thermodilution and by each Doppler echocardiographic method are displayed for each study patient i n T a b l e I. P a t i e n t s a r e l i s t e d in o r d e r f r o m t h e lowe s t (53 b e a t s / r a i n ) t o t h e h i g h e s t (123 b e a t s / r a i n ) h e a r t r a t e . E i g h t o f 17 a d u l t s h a d h e a r t r a t e s < 7 0 b e a t s / r a i n . M e a n v a l u e s for e a c h p a r a m e t e r a r e shown at the bottom under each column of data. Cardiac output determinations by the thermodilut i o n t e c h n i q u e w e r e 2.8 t o 8.7 ( m e a n = 5.5) L / r a i n . A l l
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diac output (COzcho-S through4)
versus
thermal dilution cardiac output (COTD). See text for details.
echocardiographic techniques underestimated thermodilution cardiac output; underestimation was less when Methods No. 3 or 4 were utilized. Fig. 2 shows the results of cardiac output by thermodilution on the X axes versus cardiac output by echocardiographic Methods No. 1 to 4 (see below) on the Y axes. There was a good correlation between thermodilution and echocardiographic cardiac output determinations predicted by the method of Fisher et al. (Echo-l: r = 0.89; SEE = 0.75 L/min). To simplify the calculation, the average CF was used as a constant to calculate cardiac output from the same heart rate, maximum orifice area, and velocitytime integral (Echo-2). The right upper panel of Fig. 2 shows a good correlation between thermodilution cardiac output and that predicted using the average Fisher et al. correction factor (Echo-2: r---0.91; SEE = 0.51 L/rain). Although the correlation coefficients for echocardiographic methods No. 1 and 2 are similar, the standard error of the estimate was markedly smaller when the average correction factor was utilized. The left lower panel of Fig. 2 shows a good correlation between thermodilution and Echo-3 cardiac output data, in which individual early and late diastolic M-mode data were utilized (Echo-3: r --- 0.94; SEE = 0.46 L/min). As shown in the right lower panel of Fig. 2, there was a good correlation between thermodilution and Doppler echocardiographic cardiac output determinations calculated using the average early and late diastolic M-mode data (Echo-4: r = 0.91; SEE = 0.58 L/min). As shown by the bar graph in Fig. 3, Echo-1 underestimated cardiac output by an average of 34 % in the eight patients with heart rates <70 beats/min and by
an average of 15% in the nine patients with heart rates >70 beats/min. Echo-2 underestimated output by 21% in adults with slow heart rates and by 23 % in those with heart rates >70 beats/min. The differences between Echo-1 and Echo-2 in both groups of patients were statistically significant. Echo-3 underestimated thermodilution cardiac output by an average of 10 To and 15 % for patients with heart rates that were <70 and >70 beats/min, respectively. This represented a statistically significant reduction in underestimation of output compared with Echo-1 and Echo-2 methods at heart rates <70 beats/rain and to Echo-2 at heart rates >70 beats/min. There were no significant differences in mean cardiac output determinations between patients with heart rates <70 or >70 beats/min when Echo-3 and Echo-4 were compared. DISCUSSION
In the course of assessing the method of Fisher et al. in adults, we found that cardiac output was markedly underestimated at heart rates <70 beats/rain. Their approach assumes that mean velocity and cross-sectional area can be used to quantify mitral valve cardiac output. Accurate quantification of stroke volume at the mitral valve orifice must consider that both velocity and cross-sectional area are pulsatile and thus change continuously throughout diastole. Stroke volume is the sum of all the instantaneous velocity-time integral (VTi) and cross-sectional area (Ai) products measured during diastole: SV = E (VTi) (Ai). The Fisher equation, which: uses a single diastolic velocity-t/me integral and mean cross-sectional area, fails to account for conditions in
V o l u m e 119
Cardiac output by rnitral Doppler-echo
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mid-diastole when cross-sectional area may remain large despite minimal blood flow across the mitral valve. Data from a patient whose heart rate was <70 beats/min are shown in the middle and right panels of Fig. 1. It is important to note that the mitral valve orifice remains open in mid-diastole despite the fact that there is little or no flow across the valve. Because the method of Fisher et al. determines average crosssectional area of the valve orifice during all of diastole and not just when there is flow across the valve, it underestimates cross-sectional area present during early and late diastole when velocities are highest. Thus any mitral valve method that does not utilize instantaneous cross-sectional area times instantaneous velocity products will theoretically underestimate true mitral valve flow rate. This will be most marked if the heart rate is slow enough to allow flow to approach 0 in middle diastole when the mitral leaflets remain open. Such conditions are theoretically present at both the mitral valve orifice and the mitral anulus and should lead to inaccuracy at both sites in patients with slower heart rates. In our eight patients with heart rates <70 beats/ min, Doppler tracings documented a mid-diastolic period of mitral valve velocities of <10 cm/sec. During this time the mitral anterior and posterior leaflets remained partially opened in all patients. Similar diastasis has been documented in animal preparations in which an electromagnetic flow meter confirmed 0 flow at a time when mitral leaflets were partially opened, s Recently, Binkley et al. 9 confirmed these observations in adults with bradydysrhythmias using combined Doppler and imaging echocardiography. Although the heart rates in the study of Fisher et al. are not stated, it can be assumed that they were
>70 beats/min because the experiments involved dogs and children. Stewart et al. 1~confirmed the accuracy of Fisher's method in a similar canine model and calculated an average M-mode correction factor of 0.68, identical to the one we measured using the Fisher technique. In their experiments, results with the average correction factor did not differ from those derived using individual correction factors, and they concluded that M-mode echocardiography was not necessary, Two other simplifications of the method of Fisher et al. have been proposed. Lewis et al. 11 used maximum mitral anulus area in diastole and flow velocity integral at the same site, which was found to be accurate when compared with thermodilution determinations in hospitalized patients. Meijboom et al. 12 studied a similar method in a dog model and in children. This technique used mitral anulus area calculated from two-dimensional echocardiograhic annular diameters in the apical views as did Lewis et al., but flow velocity integral was measured distal to the mitral leaflet tips in the left ventricular inflow area. Their method correlated well with the method of Fisher et al. in the dog model and with thermodilution cardiac output determinations in the children. Although the above studies suggest that M-mode echocardiography is not necessary for the accurate estimation of cardiac output at the mitral area, none of them addressed the issue of heart rate effects on the measurements. H e a r t rate probably is not the only source of error in the mitral Doppler cardiac output estimations. Measuring mitral valve orifice area by two-dimensional ech0cardiography is challenging in many adults. Interestingly, the mitral anulus method of Lewis et al. 11 resulted in less underestimation of cardiac output despite the fact that mitral orifice area
910
Miller, Richards, and Crawford
was a s s u m e d to be c o n s t a n t t h r o u g h o u t diastole. Alt h o u g h h e a r t rate d a t a were n o t provided in this study, p e r h a p s other errors offset the p r o b l e m of using a fixed orifice during the period of low flow in mid-diastole. Lateral resolution problems at the great d e p t h of the anulus in apical views or errors due to assuming a circular shape of the anulus m a y have i n t r o d u c e d offsetting errors. Also, velocity is generally lower at the anulus as Compared with the leaflet tips, as Lewis et al. 11 noted. Since accurate velocity m e a s u r e m e n t s d e p e n d on the angle of the Doppler b e a m to the flow stream, a n y error i n t r o d u c e d by assuming a zero angle m a y be increased in areas of low velocity. U n d e r e s t i m a t i o n of velocity in early and late diastole m a y increase average flow calculations from an a s s u m e d fixed orifice. Only a s t u d y using multiple i n s t a n t a n e o u s velocity and orifice area meas u r e m e n t t h r o u g h o u t diastole comparing the various m e t h o d s would answer these questions. In conclusion, our investigation supports the usefulness of the m e t h o d of Fisher et al. in estimating cardiac o u t p u t using the mitral valve orifice site in adults, and confirms t h a t M - m o d e echocardiographic images of the mitral orifice are n o t required to calculate cardiac output. However, it identifies patients with h e a r t rates of <70 b e a t s / m i n as individuals in w h o m cardiac o u t p u t can be significantly underestim a t e d if the mid-diastolic cross-sectional area of the mitral orifice is included in the correction factor used to estimate m e a n mitral cross-sectional area from the m a x i m u m area. T h u s a c o n s t a n t of 0.77 (not 0.68) should be used to estimate m e a n from m a x i m u m mitral orifice cross-sectional area in adults, because it considers the often slow h e a r t rates e n c o u n t e r e d in adults with cardiac disease. REFERENCES
1. AlversonDC, Eldridge M, Dillion T, Yabek SM, Berman W Jr. Noninvasive pulsed Doppler determination of cardiac output in neonates and children. J Pediatr 1982;101:46-50.
April 1990 American Heart Journal
2. Fisher DC, Sahn DJ, Friedman MJ, Larson D, Valdes-Cruz LM, Horowitz S, Goldberg SJ, Allen HD. The effect of variations on pulsed Doppler sampling site on calculation of cardiac output: an experimental study in open-chest dogs. Circulation 1983;67:370-6. 3. Goldberg SJ, Sahn DJ, Allen H, Valdes-Cruz LM. Evaluation of pulmonary and systemic blood flow by two-dimensional echo Doppler using fast Fourier transform spectral analysis. Am J Cardiol 1982;50:1394-400. 4. Huntsman LL, Stewart DK, Barnes SR, Franklin SB, Coloeousis JS, Hessel EA. Noninvasive Doppler determination of cardiac output in man. Clinical validation. Circulation 1983;67:593-602. 5. MeijboomEJ, Horowitz S, Valdes-Cruz LM, Sahn DJ, Larson DF, Olivera Lima C. A Doppler echocardiographicmethod for calculating volume flow across the tricuspid valve: correlative laboratory and clinical studies. Circulation 1985;71:551-6. 6. Fisher DC, Sahn DJ, Friedman MJ, Larson D, Valdes-Cruz LM, Horowitz S, Goldberg SJ, Allen HD. The mitral valve orifice method for noninvasive two-dimensional echo Doppler determinations of Cardiac output. Circulation 1983;67:872-7. 7. Loeber CP, Goldberg SJ, Allen HD. Doppler echocardiographic comparison of flows distal to the four cardiac views. J Am Co]l Cardiol 1984;4:268-72. 8. Meisner JS, McQueen DM, Ishida Y, Vetter HO, Bortolotti U, Strom JA, Frater RWM, Peskin CS, Yellin EL. Effects of timing of atrial systole on LV filling and mitral valve closure: computer and dog studies. Am J Physiol 1985;249:H604-19. 9. Binkley PF, Bonagura JD, Olson SM, Boudoulas H, Wooley CF. The equilibrium position of the mitral valve: an accurate model of mitral valve motion in humans. Am J Cardiol 1987;59:109-13. 10. Stewart WJ, Leng J, Mich R, Pandian N, Guerrero JL, Weyman AE. Variable effects of changes in flow rate through the aortic, pulmonary and mitral valves on valve area and flowvelocity: impact on quantitative Doppler flowcalculations. J Am Coll Cardiol 1985;6:653-62. 11. Lewis JF, Kuo LC, Nelson JC, Limacher MC, Quinones MA. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation 1984;70:425-31. 12. MeijboomEJ, Horowitz S, Valdes-Cruz LM, Larson DF, Born N, Rijsterborgh H, Olivera Lima C, Sahn DJ. A simplified mitral valve method for two-dimensional echo Doppler blood flowcalculation:Validation in an open-chest canine model and initial clinical studies. AM HEARTJ 1987;113:335-40.