Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window

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1 DIAGNOSTIC METHODS DOPPLER ECHOCARDIOGRAPHY Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window JANNET F. LEWIS, M.D., LAWRENCE C. Kuo, M.D., JEAN G. NELSON, R.D.M.S., MARIAN C. LIMACHER, M.D., AND MIGUEL A. QUINONES, M.D. ABSTRACT Two methods of measuring stroke volume and cardiac output with pulsed Doppler twodimensional echocardiography were developed and validated against the thermodilution technique in 39 patients, of which were in an intensive care unit. With the use of the apical four-chamber view, a mitral inflow method combined the velocity of left ventricular inflow at the mitral anulus with the crosssectional area of the anulus calculated from its diameter at middiastole (area = z r2). From the apical five-chamber view a left ventricular outflow method combined the velocity of left ventricular outflow with the cross-sectional area of the aortic anulus calculated from its diameter during early systole (parastemal long-axis view). Measurements with the mitral inflow and left ventricular outflow methods were obtained in 35 of 39 (90%) and 39 of 39 (100%) patients, respectively. Validation of the mitral method excluded patients with mitral regurgitation (n = 11) and validation of the left ventricular outflow method excluded those with aortic regurgitation (n = 4). Good correlations were observed between thermodilution and Doppler measurements of stroke volume and cardiac output for both the mitral anulus method (R =.96 and.87, respectively) and the left ventricular outflow method (R =.95 and.91, respectively). The results of the two methods correlated well with each other in patients without regurgitant valve lesions. A greater interobserver variability was observed with the mitral anulus method, which was related solely to greater variability in measuring the annular diameter. In patients with mitral regurgitation, left ventricular inflow volume was always greater than left ventricular outflow stroke volume while the inverse was true in those with aortic regurgitation. Thus, stroke volume and cardiac output can be accurately measured from the cardiac apex with mitral inflow or left ventricular outflow methods when applicable. Comparison of volumes obtained with these two methods may prove valuable in quantitating the severity of mitral or aortic regurgitation. Circulation 70, No. 3, , RECENT technological developments have made possible the application of Doppler echocardiography to the measurement of stroke volume and cardiac output. Methods previously validated consist of measuring ascending aortic flow from the suprasternal window or pulmonary arterial flow from the parasternal window.1-' These methods work on the premise that the velocity of blood flow determined from the Doppler From the Section of Cardiology, Baylor College of Medicine, The Methodist Hospital, Houston. Computational assistance was provided by the CLINFO Project, funded by grant RR-00350, Division of Research Resources, National Institute of Health, Bethesda. Address for correspondence. Miguel A. Quinones, M.D., Section of Cardiology, The Methodist Hospital, 6535 Fannin -MS, F-1001, Houston, TX Received Jan. 9, 1984; revision accepted April 26, Presented at the 56th Annual Scientific Sessions of The American Heart Association, November 1983, Anaheim, CA. Vol. 70, No. 3, September 1984 shifts of the reflected sound waves are uniformly distributed throughout the cross section of the vessel so that the product of the area under the velocity curve times the cross-sectional area of the vessel is equal to the volume of blood passing through the vessel. Among other factors, the velocity profile within a vessel and the accuracy of the measurements of the cross-sectional area of the vessel affect the accuracy of Doppler flow measurements. For instance, in patients with aortic sclerosis or stenosis the velocity profile in the ascending aorta becomes nonlaminar and a greater dispersion of velocities is observed within the vessel, invalidating the use of ascending aortic flow velocity for measuring cardiac output. When pulsed Doppler echocardiography is used, the vessel cross-sectional area should ideally be measured at the site of sample volume position for greater accuracy. Images adequate 425

2 LEWIS et al. for determination of cross-sectional area of the pulmonary artery from the parasternal window or of the ascending aorta from the suprasternal notch cannot always be obtained in adult patients, thus limiting the applicability of these techniques in clinical practice. The cardiac apex provides access to the evaluation of flow velocities through both mitral and aortic valves with minimal angulation between flow and the ultrasound beam and, theoretically, may be ideal for flow calculations. Recently, Fisher et al.8 accurately measured mitral inflow volume from the cardiac apex in experimental animals. They recorded mitral inflow velocity in the left ventricle just distal to the mitral valve leaflets and calculated a mean mitral valve area by combining the maximal area of the valve orifice visualized from a parasternal short-axis view with an M mode tracing of the valve motion. In this investigation we have developed and validated two other approaches to measuring intracardiac flows from the apical window: (1) a modification of Fisher's method for measuring mitral inflow consisting of placing the sample volume at the level of the mitral anulus and (2) a left ventricular outflow method with the sample volume positioned at the aortic anulus immediately proximal to the aortic valve leaflets. We have found that results of both methods correlate well with measurements by thermodilution and that both are applicable to a large number of critically ill adult patients. Methods Clinical population. The clinical population consisted of 39 patients, 10 women and 29 men, whose ages ranged from 35 to 86 years and who had undergone determination of cardiac output by thermodilution either while in an intensive care unit or as part of diagnostic cardiac catheterization. In none of the patients was clinical, echocardiographic, or Doppler evidence of aortic or mitral stenosis found. Thirty-three patients were studied while in the intensive care unit being treated for either a myocardial infarction or severe congestive heart failure. In the majority of patients the clinical diagnosis (table 1) was coronary artery disease. Mitral regurgitation, diagnosed by Doppler echocardiography as a systolic wide frequency dispersion in the left atrium behind the mitral valve, was present in 11 patients, and aortic regurgitation, detected as a diastolic wide frequency dispersion in the left ventricular outflow, was present in four patients. All of the echocardiographic studies were performed within minutes before the determination of cardiac output by thermodilution. Both the two-dimensional imaging and the Doppler studies were done with an Electronics for Medicine/Honeywell sector scanner equipped with 2.25 and 3.5 MHz mechanical transducers that oscillate through an angle of 60 to 75 degrees. The system has a movable cursor that allows Doppler sampling anywhere along the plane of the image. When the Doppler mode is activated, the transducer stops oscillating, the last visualized two-dimensional image is frozen, and the crystal is converted fully into a pulsed Doppler system. The depth of the sample volume is adjustable to a maximum of 16 cm from the trans- 426 ducer and the length of the volume is adjustable from 2 to 20 mm (set at 5 mm for this investigation). The two-dimensional image is updated automatically every fifth cardiac cycle to allow maintenance of the sample volume in the desired position. In addition to the audio output, the frequency shifts (AF) are processed through a fast-fourier transform spectral analyzer and expressed graphically as flow velocity (V) by solving the Doppler equation: AF X Vm 2Fo x CosO where Vm = the speed of sound in the medium (1540 M/sec); Fo = emitting frequency of the transducer; 0 the angle of = incidence between sound waves and flow. When solving the Doppler equation the instrument assumes that 0 = 0 (cos ). However, within the plane of the two-dimensional image, this angle may be estimated with a movable cursor and corrections to the above equation can be made if desired (see below). Each patient was examined while in a lateral recumbent position, with the transducer at the point of the apical impulse or slightly to the left of this area. The transducer was manually rotated to obtain an apical four-chamber view of the heart that provided good visualization of the left ventricular cavity with maximal excursion of the mitral valve leaflets. The sample volume was placed at the level of the mitral valve anulus with the cursor line oriented as parallel as possible to an imaginary line transversing the left ventricle from apex to mitral valve (figure 1). Slight adjustments in transducer angulation or sample volume position were at times required to maximize the audio and graphic quality of the Doppler signal. The velocity of mitral inflow was recorded over several cardiac cycles at a paper speed of 100 mm/sec. The position of the sample volume was moved slightly from one corner of the anulus to the other in the majority of studies so that any significant change in morphology or amplitude of the velocity tracings that would suggest a nonlaminar velocity profile could be detected; this was not observed in any patient. The sample volume was then gradually moved through the leaflets and into the inflow region of the left ventricle to ensure the absence of inflow stenosis appearing as a highvelocity flow disturbance with frequency dispersion. Although inflow stenosis was not present in any of the patients studied, it was not uncommon to see a modest increase in peak early diastolic velocity (for example from 50 to 70 cm/sec) when sampling in the left ventricular inflow region. The magnitude of this increase was greater in patients with low cardiac output and poor mitral leaflet separation. For the recording of left ventricular outflow, the transducer was rotated slightly with a superior tilt until the aortic valve and the ascending aorta were visualized and the sample volume was placed in the middle of the left ventricular outflow immediately proximal to the leaflet of the aortic valve (figure 2). As with the mitral inflow method, slight adjustments in either transducer or cursor angulation were at times required to optimize the orientation between the sound waves and flow. This was assessed by the quality of the Doppler tracing. However, once this position was obtained, minimal displacement of the sample volume laterally did not appear to influence the morphology or amplitude of the flow-velocity curve. Several cycles of left ventricular outflow velocity were recorded at a paper speed of 100 mm/sec. The possibility of aortic stenosis was excluded by placing the sample volume through the aortic valve and in the ascending aorta using the parasternal and suprasternal windows and searching for wide systolic frequency dispersion of the flowvelocity curve as an indicator of stenosis. Finally, the transducer was placed in the parasternal position to obtain a long-axis view (1) CIRCULATION

3 DIAGNOSTIC METHODS-DoPPLER ECHOCARDIOGRAPHY of the left ventricle and the aortic valve, as shown in figure 2. (time-velocity integral) by the cross-sectional area of the mitral This view was selected over the apical view because the struc- anulus. Curves from five to 10 cardiac cycles were digitized tures needed for adequate measurements of the aortic anulus following the contour of the darkest portion of the velocity were not always properly visualized from the apical window. tracing and an average of the time-velocity integrals was ob- Measurements and calculations. All measurements were tained. made with the aid of an off-line computerized-analysis station The middiastolic transverse diameter of the mitral anulus was equipped with internal calipers and a programmable graphic measured from the second or third video frame after the initial analyzer (Digisonics EC-200). The recorded two-dimensional maximal opening motion of the anterior leaflet. Measurements images ('/2 inch VHS) were played back through a videocassette were taken from the inner edge of the lateral bright corner of the system equipped with a frame-by-frame bidirectional search anulus to the inner edge of the medial corner just below the module (JVC BR6400 U). insertion of the mitral leaflets (figure 1). Measurements from a Mitral inflow method. The mitral inflow volume was deter- minimum of five cardiac cycles were averaged and the crossmined by multiplying the area under the diastolic inflow curve sectional area of the anulus was derived as FT x r2, where r TABLE 1 Doppler and thermodilution data Patiente Doppler mitral Doppler LVO Thermodilution No. Age/sex Dx CSA TVI SV CO CSA TVI SV CO sv CO 1 48 M CRF 2 62 M CAD 3 58 M CAD 4 56 M AMI 5 64 M AMI 6 53 M CAD 7 68 M AMI 8 77 M CM 9 65 M CAD F CAD M CAD F CAD M CAD M CAD F HTN M AMI M AMI M AMI M AMI M AMI F HTN M CM M AMI F CAD M CAD/MR M AMI/MR F AMI/MR M CAD/MR F CAD/MR M CAD/MR F MR M MR 67 F MR M MR M MR M AR F AR 35 M AR M AR Dx = diagnosis; LVO = left ventricular outflow; CSA = cross-sectional area; TVI = time-velocity integral; SV stroke volume; CO cardiac output; CRF = chronic renal failure; CAD = coronary artery disease; AMI = acute myocardial infarction; CM = cardiomyopathy; HTN hypertension; MR = mitral regurgitation; AR = aortic regurgitation. 427 Vol. 70, No. 3, September

4 LEWIS et al. C.CS JLL CORR 4cf*/3 } A 1 t i FIGURE 1. Apical four-chamber view of the heart with the sample volume (SV) positioned at the plane of the mitral anulus, indicated by the large arrows. The Doppler cursor is aligned parallel to mitral inflow. The Doppler recording of flow velocity is shown at a paper speed of 100 mm/see. The time-velocity integral (TVI) is derived by digitizing the velocity curve as outlined on left atrium; RA the second cardiac cycle. LV left ventricle; LA right atriulm. = represents half of the annular diameter. This method assumes a circular shape for the mitral anulus and a constant cross-sectional area throughout diastole. In normal subjects. Ormiston et al.9 performed a two-dimensional echocardiographic reconstruction of the mitral anulus = from multiple calibrated apical views and found the shape of the anulus to be nearly circular during diastole. A 12% gradual increase in cross-sectional area was observed from early diastole to end-diastole. In the first 15 patients the cross-sectional area of the mitral FIGURE 2. Still-frame images ot the heart during systole in the parasternal long -axis view (tojp lcft), showing where the aortic anulus diameter is measured (white arrow), and in the apical five-chamber view (tolp right), illustrating the position of the sample volume immediately proximal to the aortic valve. Doppler recording of left ventricular outflow velocity is shown in the I/oer paniel at a paper speed of 100 mm/sec. AV - aortic valve; Ao = ascending aorta; other abbreviations as in figure CIRCULATION

5 DIAGNOSTIC METHODS-DOPPLER ECHOCARDIOGRAPHY anulus was also derived by combining annular diameters (D) from the four-chamber and two-chamber apical views as (w x D, x D2)/4. The results were nearly identical to those derived from the four-chamber view alone and therefore the single measurement method was selected for the investigation in order to increase the clinical applicability of the method. Stroke volume (SV) was calculated as SV = TVI x M-CSA (2) where M-CSA is the cross-sectional area of the mitral anulus. Cardiac output was calculated as SV x heart rate derived from the five to 10 cardiac cycles digitized. Left ventricular outflow method. Left ventricular outflow volume was determined as the product of the time-velocity integral (average of five to 10 cardiac cycles) and the crosssectional area of the aortic anulus. The outflow velocity curves were digitized following the contour of the darkest portion of the curve in a manner similar to the mitral inflow method. The cross-sectional area of the aortic anulus was calculated as 7w x r2, where r represents half of the annular diameter (average of five to 10 cardiac cycles) measured immediately proximal to the points of insertion of the aortic leaflets one or two video frames after maximal systolic leaflet separation (figure 2). Whenever possible, the aortic anulus was also imaged in the short-axis plane, confirming its circular shape and the lack of significant change in size during systole. However, the diameter measured from the parasternal long-axis plane was used to calculate the annular cross-sectional area in order to increase the success rate in patients in whom there were technical difficulties. Correction for angle. As evident by equation 1, the angle of incidence between blood flow and sound is an important determinant of the accuracy of Doppler measurements of blood velocity, and ideally it should either be zero or well known. In practice, this angle cannot be measured precisely from a twodimensional image for two reasons. First, total flow within a vessel or through an orifice is not seen, and therefore, to measure an angle it has to be assumed that flow is directed parallel to a visualized anatomic landmark, such as the walls of the aortic root or the long-axis plane of the ventricle. Second, in a given two-dimensional plane the angle may be significantly underestimated due to the orientation of the sound waves with flow on the orthogonal (nonvisualized) plane. Fortunately, 0 can vary by as much as 20 degrees with an error in underestimating flow velocity of no more than 6%. Use of the apical window has the advantage of providing a shallow ('20 degrees) angle between the sound beam and both mitral inflow and left ventricular outflow (figures 1 and 2). Thus, during this investigation we elected not to correct for the angle but rather to optimize transducer angulation so that the transducer would be as parallel to flow as possible. Interobserver variability. All measurements and calculations were done by an observer with no knowledge of the thermodilution data. To test interobserver variability all the measurements in 15 patients were repeated by a second observer. This variability was expressed as a percent error for each measurement and was determined as the difference between the two observers divided by the mean value of the two observations. Thermodilution-derived cardiac output. The thermodilution cardiac outputs were obtained with an Edward cardiac output instrument model 9520-A by injecting 10 ml of 5% dextrose in water at 0 C through the proximal port of a thermodilution Swan-Ganz catheter placed in the main pulmonary artery of each patient. Cardiac output was computed as the average of several determinations. If the difference between the lowest and highest value of the first three determinations was Vol. 70, No. 3, September 1984 less 10%, the average of the three was taken. If the difference was more than 10%, two more outputs were obtained and the values at the two extremes were discarded before averaging. Stroke volume was calculated as cardiac output divided by heart rate. Data were analyzed by linear regression analysis. Results Table 1 lists the data obtained for each of the patients studied and the statistical correlations are shown in table 2. The mitral inflow method could not be used in four patients because the quality of the two-dimensional images was not adequate for measurements of mitral annular diameter. The left ventricular outflow method was successfully applied in all patients. Mitral inflow vs thermodilution. In 24 patients with clinically adequate mitral inflow measurements and without Doppler evidence of mitral regurgitation, a high correlation was observed between thermodilution-derived stroke volume and Doppler-determined mitral inflow volume over a wide range of stroke volumes, with an R value of.96 and an SEE of 5.9 ml (figure 3, A). There was no consistent over- or underestimation of thermodilution stroke volume by the Doppler method, as shown by the regression equation y = 0.91x Comparison of cardiac outputs obtained with the two methods revealed an R value of.87 and an SEE of 0.59 liters/min. Left ventricular outflow vs thermodilution. In the 35 patients without aortic insufficiency a high correlation was observed between thermodilution stroke volume and Doppler-determined left ventricular outflow volume over a wide range of stroke volumes, with an R value of.95 and an SEE of 6.4 ml (figure 3, B). As with the mitral method, the regression equation (y = 0.91x + 7.8) indicated no significant over- or underestimation of stroke volume by the Doppler method. Cardiac output determined by the Doppler left ventricular outflow method correlated with that by thermodilution cardiac output, with an R value of.91 and an SEE of 0.63 liters/min. TABLE 2 Linear regression analysis Regression y vs x n R SEE equation TD-SV MVI-SV ml y = 0.91x TD-CO MVI-CO /min y = 0.80x TD-SV LVO-SV ml y = 0.91x TD-CO LVO-CO /min y = 0.85x MVI-SV LVO-SV ml y = 1.05x MVI-CO LVO-CO /min y = 0.89x TD = thermodilution; SV stroke volume; MVI = mitral valve inflow; CO = cardiac output; LVO = left ventricular outflow. 429

6 LEWIS et al. TD-SV (cc) lotr- 80 F 60F 40 F 20 F A 0 0* - S R= 0.96, n= 24 SEE= 5.9 cc y= 0.91X loor F B 1~~~~~~~~~~.1, A,-'.S*..I /,/ * R= 0.95, n= 35 SEE= 6.4 cc. v~~~~= n al- L 7 Q ol IoILI }O I I Y` U.1x MVI-SV (cc) LVO-SV (cc) FIGURE 3. Correlations between thermodilution (TD) and Doppler measurements of stroke volume (SV) using A, the mitral inflow method (MVI) and B, the left ventricular outflow method (LVO). The broken lines indicate the 95% confidence limit of the regression. Mitral inflow vs left ventricular outflow. In the 20 patients with technically adequate mitral and left ventricular outflow measurements and without evidence of mitral or aortic regurgitation by Doppler echocardiography, the stroke volumes determined by the two Doppler methods correlated well with each other, with an R value of.95 and an SEE of 6.6 ml. Likewise, cardiac output determinations with the two methods correlated, with an R value of.87 and an SEE of 0.64 liter/min. Neither method appeared to consistently yield results higher or lower than the other method. Interobserver variability. The percent error between the two observers for the different measurements are listed in table 3 as the means + SD. The variability in measuring the time-velocity integral was low for both the mitral and the left ventricular outflow methods. On the other hand, a larger error was observed in the determination of the cross-sectional area of the mitral anulus (14.8%) when compared with the aortic anulus (6.0%). This increased variability in measurement of the mitral anulus resulted in a larger interobserver error in the measurement of stroke volume by the mitral method (16.4%) than by the left ventricular outflow method (6.8%). Discussion This investigation clinically validates the use of Doppler-determined flow velocity through the mitral anulus or left ventricular outflow to calculate stroke volume and cardiac output in patients without stenotic or regurgitant lesions of the respective valves. The primary advantage of this approach is the higher yield of technically satisfactory studies in critically ill patients since the apical window allows visualization of most of the structures involved in the measurements and provides an optimal angle between the sound waves and flow Both methods used in this study assumed uniform velocities within the mitral or aortic anulus. At low velocities, flow is usually laminar.11 In addition, the velocity profile tends to flatten as blood converges into the inlet of a conduit (such as from left atrium to mitral anulus) and during rapid acceleration, e.g., during early ejection through the aortic anulus. In this study we did not observe significant changes in velocity as we moved the sample volume laterally within the area of the mitral or aortic anulus and the dispersion of velocities was minimal. Thus, it appears that the velocity profile within the normal mitral and aortic anulus were appropriate for determination of blood flow by Doppler echocardiography. Most Doppler methods assume that the cross-sectional area at which the sample volume is placed remains unchanged during the time period of flow. When Doppler sampling is done in the left ventricular inflow distal to the mitral valve leaflets, the velocity of flow may be altered by instantaneous changes in the size of the valve orifice. Fisher et al.8 therefore derived a "mean mitral area" by combining two-dimensional imaging of the orifice of the valve with a mean leaflet diastolic separation derived from the M mode echocardiogram and were able to accurately compute cardiac output in an experimental model. Unfortunately all the measurements required to apply their method are fre- TABLE 3 Interobserver variability Mean percent error ( SD) Mitral method LV outflow method CSA TVI SV/CO Abbreviations are as in table 1. CIRCULATION

7 DIAGNOSTIC METHODS-DOPPLER ECHOCARDIOGRAPHY quently difficult to obtain in many adult patients, particularly in the critically ill. In this investigation we assumed that flow through the mitral anulus was dependent mostly on the crosssectional area of the anulus and less on the mobility of the valve leaflets. In fact, we frequently observed an increase in inflow velocity as the sample volume was passed through the valve orifice into the body of the left ventricle and the magnitude of this increase was greater in patients with low cardiac outputs, suggesting that this assumption was correct. Although an increase in anular area averaging 12% has been documented from early to end-diastole by Ormiston et al.,9 this change represents a relatively small change in diameter since it is related to the square root of area. The method described by Ormiston for measuring mitral annular area is complex, time consuming, and technically applicable to a small subgroup of patients studied. Thus, at present, the only practical alternative is to calculate the area from a diameter measurement. In our initial efforts we did not find any significant difference between the use of two orthogonal diameters of the mitral anulus vs the use of one derived from the apical fourchamber view, and therefore we selected this simplified approach in order to increase the clinical applicability of the method. The results correlated well with those obtained with the thermodilution method. There are potentially fewer theoretical problems with the left ventricular outflow method since the aortic anulus is indeed circular and its size changes minimally during ejection. We again used one diameter measurement from a long-axis view in order to simplify the technique and make it more clinically applicable. The results with the left ventricular outflow method were equal in accuracy to those with the mitral anulus method. However, this method was easier to apply in all patients and, importantly, involved less interobserver variability than the mitral anulus method. An additional advantage of these two new Doppler methods of measuring stroke volume and cardiac output is the potential for calculating regurgitant volumes by comparing one to the other in patients with isolated mitral or aortic regurgitation. As shown in table 1, the mitral inflow volumes were greater than the left ventricular outflow volumes in all patients with mitral regurgitation, while the inverse was true in the patients with aortic regurgitation. A regurgitant fraction could therefore be calculated as the difference between the results of the two Doppler methods divided by the volume derived from the respective regurgitant valve. Future clinical studies are needed to validate this new Doppler approach against hemodynamic-angiographic calculations of regurgitant fractions. The increased clinical yield provided by these two new methods should expand the applicability of Doppler echocardiography for measuring cardiac output in routine clinical practice. We acknowledge the secretarial assistance of Almanubia Cespedes. References 1. Huntsman LL. Stewart DK, Barnes SR, Franklin SB, Colocousis JS, Hessel EA: Noninvasive Doppler determination of cardiac output in man. Circulation 67: 593, Goldberg SJ, Sahn DJ, Allen HD, Valdes-Cruz LM, Hoenecke H, Carnahan Y: Evaluation of pulmonary and systemic blood flow by 2-dimensional Doppler echocardiography using fast Fourier transform spectral analysis. Am J Cardiol 50: 1394, Alverson DC, Eldridge M, Dillon T, Yabek SM, Berman W Jr: Noninvasive pulsed Doppler determination of cardiac output in neonates and children. J Pediatr 101: 46, Distante A, Moscarelli E, Rovai D, L'Abbate A: Monitoring of changes in cardiac output by transcutaneous aortovelography, a non-invasive Doppler technique: comparison with thermodilution. J Nucl Med Allied Sci 24: 171, Loeppky JA, Greene ER, Hoekenga DE, Caprihan A, Luft UC: Beat-by-beat stroke volume assessment by pulsed Doppler in upright and supine exercise. J Appl Physiol 50: 1173, Magnin PA, Stewart JA, Myers S, von Ramm 0, Kisslo JA: Combined Doppler and phased-array echocardiographic estimation of cardiac output. Circulation 63: 8, Schuster AH, Nanda NC: Doppler echocardiography and cardiac pacing. PACE 5: 607, 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 67: 872, Ormiston JA, Shah PM, Tei C, Wong M: Size and motion of the mitral valve annulus in man. I. A two-dimensional echocardiographic method and findings in normal subjects. Circulation 64: 113, Hatle L, Angelsen B: Doppler ultrasound in cardiology, ed 1. Philadelphia, 1982, Lea & Febiger, p Hatle L, Angelsen B: Doppler ultrasound in cardiology, ed 1. Philadelphia. 1982, Lea & Febiger, p 18 Vol. 70, No. 3, September