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Comparison of Continuous Left Ventricular Volumes by Transthoracic Two-Dimensional Digital Echo Quantification with Simultaneous Conductance Catheter Measurements in Patients with Cardiac Diseases
Comparison of Continuous Left Ventricular Volumes by Transthoracic Two-Dimensional Digital Echo Quantification With Simultaneous Conductance Catheter Measurements in Patients With Cardiac Diseases Chen-Huan Chen, MD, Erez Nevo, MD, DSc, Barry Fetics, BE, Masaru Nakayama, MD, PhD, Peter H. Pak, MD, W. Lowell Maughan, David A. Kass, MD
MD,
and
Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 6 15 years, range 22 to 70; ejection fraction 63 6 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter 5 slope z DEQ 1 intercept, slope 5 0.94 6 0.09, inter-
cept 5 5 6 8 ml, r2 5 0.86 6 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 6 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. Enddiastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 6 0.31, mean intercept 14 6 37 ml, average r2 5 0.89 6 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 6 0.43, intercept 5 220 6 26 ml, r2 5 0.67 6 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans. Q1997 by Excerpta Medica, Inc. (Am J Cardiol 1997;80:756 –761)
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angiography,8 ultrafast computed tomography,11 thermodilution,5 3-dimensional reconstructions,12 and simultaneous aortic flow measurements.4 The only study evaluating the dynamics of the LV volume signal compared short-axis area curves during a steady-state cycle with those measured by nonsimultaneous ultrafast computed tomography,11 and reported systematic errors in estimating end-systolic and end-diastolic areas. To date, echocardiographic continuous LV volumes derived by conventional transthoracic approaches at steady state and during loading transients have not been validated against simultaneously measured LV volumes in humans. The present study was designed to test this by comparing a new transthoracic digital echo quantification method with volumes measured by intracardiac conductance catheter.
eal-time, continuous left ventricular (LV) volume can be estimated by an echocardiographic backscatter technique that detects the endocardial border and calculates the left ventricular area automatically. Such volume data are useful for determining cardiac performance parameters such as ejection fraction, pressure-volume relations,1 and maximal power indexes.2 The accuracy of steady-state stroke volume,3,4 cardiac output,5 ejection fraction,6 –9 and end-systolic and end-diastolic volumes8,10,11 determined by this technique have been evaluated by comparisons with nonsimultaneous radionuclide imaging,9 contrast LV From the Division of Cardiology, Department of Internal Medicine, Johns Hopkins University Medical Institutions, Baltimore, Maryland. Dr. Chen-Huan Chen is a Clinical Research Fellow from the Division of Cardiology, Department of Medicine, Veterans General HospitalTaipei and National Yang-Ming University, Taipei, Republic of China. This study was supported by NIA Grant AG:12249 (D.A.K.), Bethesda, Maryland; Colin Research Fellowship Award (B.F.), San Antonio, Texas; and a Fogarty Foundation Grant (E.N.)., Bethesda, Maryland. Manuscript received March 6, 1997; revised manuscript received and accepted May 21, 1997. Address for reprints: David A. Kass, MD, Halsted 500, Division of Cardiology, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, Maryland 21287.
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©1997 by Excerpta Medica, Inc. All rights reserved.
METHODS
Study subjects: Nineteen patients underwent 21 diagnostic pressure-volume loop catheterizations (2 patients underwent separate catheterizations 1 year apart). Echocardiographic images were of insufficient quality for analysis in 3 patients, and these data were 0002-9149/97/$17.00 PII S0002-9149(97)00509-2
FIGURE 1. A sample echocardiogram showing apical 4-chamber view endocardial delineation by DEQ. The region of interest is manually drawn around the left ventricle. Real-time, continuous left ventricular (LV) volume (VOL) curve is displayed in the lower panel, along with the electrocardiogram (ECG) and calculated variables, which are given as numerical values and are updated each cycle. EDV 5 end-diastolic volume; ESV 5 end-systolic volume; EF 5 ejection fraction; HR 5 heart rate; SV 5 stroke volume.
not used. Mean age of the remaining 16 patients (9 men, 7 women) was 50 6 15 years (range 22 to 70). Clinical diagnosis included coronary artery disease (2 patients), hypertensive cardiovascular disease (1 patient), hypertrophic obstructive cardiomyopathy (1 patient), dilated cardiomyopathy (1 patient), constrictive pericarditis (1 patient), and post-heart transplantation (10 patients). Ejection fraction ranged from 15% to 85% (mean 63 6 20%). Informed consent approved by the Joint Committee on Clinical Investigation was obtained from each patient. Digital echo quantification method: The digital echo quantification (DEQ, Vingmed Sound, Norway) used in this study processes raw high-quality 2-dimensional images in a 4-chamber longitudinal view, with fine gray-scale resolution obtained by a 12-bit A/D converter. Raw backscatter data are digitized, stored to memory, and subject to a dynamic processing algorithm that applies temporal and spacial digital filtering and statistically based edge-detection enhancement. A contour identifying the myocardial blood pool interface is superimposed on the real-time echocardiographic image and used for automated area calculation. Areas are transformed to volumes by combining with the ventricular long axis, which is assumed to be constant during contraction. Calculated area or volumes are displayed as a real-time trace (Figure 1), and exported as an analog signal. Procedures: In several patients, the echo image quality was severely limited due to the need for the patient to lie supine on the catheterization table. Therefore, a custom-designed radio-transparent lightweight tilting table was used. The operator could tilt the patient from 0 to 30° toward a left lateral decubitus position to enhance echocardiographic image quality. After routine coronary angiography, left ventriculog-
raphy, and right heart catheterization, a 7Fr multielectrode pressure-conductance volume catheter (SSD-767 or 768, Millar Instruments, Houston, Texas) was introduced via a femoral artery, advanced to the LV apex, and connected to stimulator microprocessor (Sigma V, CardioDynamics, Bijnsdurg, the Netherlands) to generate a volume signal.13 During acquisition of invasive pressure-volume data, echocardiographic images and DEQ processing were simultaneously obtained (model CFM 800, Vingmed Sound) using a 3.2- or 2.5MHz mechanical sector transducer. Data were acquired in standard apical 4-chamber view so the detected LV area could be directly converted to LV volume by the single-plane area-length method. Invasive high-fidelity LV pressure and volume signals from the conductance catheter, and the noninvasive LV volume derived from the DEQ analysis of the echo image were digitized simultaneously at 200 or 250 Hz, both at steady state and during preload reduction. The latter was achieved by transient intraluminal obstruction of inferior vena cava flow by balloon catheter (SP:9168, Cordis, Miami, Florida). Data analysis: Digitized hemodynamic data were analyzed off-line using custom software developed under the environment of MATLAB for Windows, version 4.2c (The MathWorks Inc). Both volume signals were digitally filtered (8 order, zero phase, Butterworth filters with a 20-Hz cutoff) to reduce noise. Respiration significantly effected transthoracic 2-dimensional echocardiographic images, and thus the DEQ volume signals showed clear respiratory variation. Signal averaging over at least 1 respiratory cycle removed this variability from steady-state data. For DEQ volume data during preload reduction, a fastFourier transformation band-stop filter was applied with cutoff frequencies (ranges 0.3 to 0.5 Hz) determined for each patient based on individual frequency of respiration. Both noninvasive and invasive volume signals were calibrated by matching the average width of the pressure-volume loop to stroke volume calculated by dividing thermodilution-derived cardiac output by heart rate.13,14 By further matching ejection fraction to that measured by contrast ventriculography, absolute calibration was achieved. The DEQ processing for calculation of echocardiographic area and volume introduced a time delay into the analog volume signal,1,11 compared with the instantaneous invasive signal derived from the conductance catheter. To adjust for this delay, which varied among patients, the 2 volume signals were aligned by matching the minimum and maximum volume time points. Catheter and DEQ-based volume signals from 10 to 15 consecutive heart cycles were averaged, and maximum and minimum points identified from the respective signal-averaged cycles. The times from the R wave of the electrocardiogram to each of these fiduciary volume-signal time points were averaged for each averaged cycle, and the difference in this averaged time was used as a measure of the delay of the METHODS/VALIDATION OF DEQ VOLUME
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volumes from the catheter and DEQ volumes were compared by linear regression analysis. To further test the clinical usefulness of the DEQ volume pressure-volume data, several variables were calculated from steady-state pressure-volume loops and from the preload-reduction pressurevolume relations. Steady-state parameters included: LV end-diastolic pressure, measured as the pressure at the right lower corner of the pressure-volume loop, peak filling rate (PFR) normalized by EDV (PFR/EDV), equal to the first derivative of the volume curve divided by EDV, and external stroke work, equal to the area within the pressure-volume loop. Parameters derived from the preload reduction data included end-systolic pressure-volume relation,15 volume intercept at zero pressure,15 and preload recruitable stroke work.16 Statistical analysis: Comparison between DEQ and conductance catheter volumes were analyzed by linear regression. Bland-Altman analysis17 was used to examine the agreement of various indexes derived from DEQ and volume catheter data, and the paired Student’s t test was used to test the mean differences.
RESULTS
Comparison of catheter and DEQ volumes at steady state: There was greater
beat-to-beat variability of the DEQ volume trace than of the catheter volume signal, demonstrated in the volumetime curves (Figure 2A) and mean 6 SD envelopes for signal-averaged volume data (Figure 2B, right panel). However, signal-averaged DEQ volume curves tracked the catheter volume curves well during an averaged cardiac cycle (Figure 2B, left panel). Maximal positive differences between DEQ and catheter volumes (Figure 2C) ranged from 6 to 27 ml (mean 16 6 8), and maximal negative differences from 238 to 24 ml (mean 214 6 9). Regression analysis between catheter and DEQ volume (Figure 2C, right panel) yielded a mean slope of 0.94 6 0.09, intercept 5 6 8 ml, and r2 5 0.86 6 0.12.
FIGURE 2. An example of the measured and analyzed data from 1 patient during steady state. A, simultaneously recorded catheter and DEQ left ventricular volumes; B (left panel), signal-averaged catheter (dotted line) and DEQ (solid line) volumes for 1 cardiac cycle; right panel, mean 1 SD and mean 2 SD boundaries for the signal-averaged catheter (dotted lines) and DEQ (solid lines) volumes. The boundaries are wider for the DEQ volume; C (left panel), point-by-point difference (solid line) and its 6 1 SD boundaries (dashed lines) of the signal-averaged catheter and DEQ volumes. Solid arrow indicates timing of maximum difference and hollow arrow indicates timing of minimum difference; right panel, linear regression analysis for the 2 signal-averaged volumes.
DEQ signal. The original DEQ data were then phaseadvanced by this amount. For steady-state recordings, the phase aligned volume signals from 10 to 15 consecutive heart cycles were averaged to generate a comparison cycle. Time courses of the averaged catheter and DEQ volume signals from each patient were compared directly by computing point-to-point difference and linear regression. To summarize the comparison for the overall study population, signal-averaged catheter and DEQ volume traces from each patient were resampled to provide 100 data points with equal spacing. The resampled catheter and DEQ volume traces were then group averaged. For recordings during inferior vena caval occlusion, end-diastolic (EDV) and end-systolic 758
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Comparison of catheter and DEQ volumes during inferior vena caval occlusion: Echo images degraded
during inferior vena caval occlusion in half of the studies due to a change in cardiac position relative to the echo probe, or to respiratory chest wall movement. Analyzable recordings of DEQ volume during inferior vena caval occlusion were obtained in the remaining 9 studies. Inferior vena caval occlusion yielded a 45 6 SEPTEMBER 15, 1997
FIGURE 3. An example of the measured and analyzed data from 1 patient during inferior vena caval obstruction. A, simultaneously recorded catheter and DEQ left ventricular volumes; B, linear regression analysis for end-diastolic volume (EDV); C, linear regression analysis for end-systolic volume (ESV); D, linear regression analysis for whole tracings.
FIGURE 4. A, an example showing steady-state pressure volume loop constructed from signal-averaged invasive left ventricular (LV) pressure and catheter (dotted line) or noninvasive DEQ (solid line) volume; B to D, Bland-Altman analysis for end-diastolic pressure (EDP) (B), peak filling rate/end-diastolic volume (PFR/EDV) (C), and external stroke work (SW) (D) calculated from the steady-state signal-averaged catheter and DEQ volumes and/or LV pressure. Dashed lines indicate mean differences; dotted lines, boundaries of 2 SDs of the differences.
13% decrease in EDV. Beat-by-beat EDV changes determined by the 2 volume methods were significantly correlated (mean slope 0.88 6 0.31, mean intercept 14 6 37 ml, average r2 5 0.89 6 0.11, each individual r2 value had a p value ,0.01) (Figure 3).
For end-systolic volumes, results were significant but displayed more scatter, with a mean slope of 0.80 6 0.43, intercept 5 220 6 26 ml, and r2 5 0.67 6 0.18, all p ,0.05. Figure 3D displays simultaneous volumevolume data for the transient data displayed in panel METHODS/VALIDATION OF DEQ VOLUME
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FIGURE 5. A and B, same sample from Figure 4 showing pressure–volume loops constructed from invasive left ventricular pressure and catheter (A) or noninvasive DEQ (B) volume. Although there were good correlations for the end-systolic/end-diastolic volumes of the volume signals, the loop shapes were not similar. Dotted lines indicate end-systolic pressure-volume relation (Ees) slope from the catheter volume; solid line, Ees slope from the DEQ volume. C and D, linear regression analysis for the Ees (C), volume intercept at zero pressure (V0) (D), and preload recruitable stroke work (PRSW) (E) calculated from left ventricular pressure and catheter or DEQ volumes during preload reduction.
A, revealing reasonable correlation throughout but wider scatter around the regression line. Hemodynamic variables derived from DEQ volume and pressure-volume data: Results of steady-state and
transient pressure-volume and volume signal analysis are shown in Figures 4 and 5. Figure 4A displays example steady-state pressure-volume loops constructed from catheter and DEQ volumes, respectively. Correlations between variables from steadystate pressure volume loops were good (Figure 4B to 4D), with no consistent bias in the estimate by DEQ method, and most of the differences falling within an acceptable range. Figure 5A to 5B shows example pressure-volume data during inferior vena caval obstruction. Conversely, there were only fair correlations for indexes derived from the preload transient data (Figure 5C to 5E).
DISCUSSION Continuous echocardiographic LV volume signals were first made available by using a backscatter technique, and have been applied to the evaluation of LV systolic1,3–10,18 –22 and diastolic function.23–25 However, this echocardiographic-derived LV volume sig760
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nal has never been directly compared with simultaneously obtained independent continuous LV volumes either at steady state or during transient changes in cardiac volume. This study performed such comparisons between a new method for real-time, continuous LV volume echo-based signal analysis (DEQ) and data measured by invasive conductance catheter. The 2 volume signals were generally well correlated, and the data could be used to construct steady-state pressure-volume loops and assess a number of useful hemodynamic indexes. However, stable DEQ images were definitely more difficult to maintain during loading transients. Whereas DEQ end-systolic and enddiastolic volumes correlated reasonably well with catheter volumes in the studies with persistent images, the derived hemodynamic indexes were less reliable. In this study, the DEQ signal was itself precalibrated by the same external standards (i.e., thermodilution cardiac output and ventriculographic ejection fraction) used to calibrate the conductance catheter signal. In contrast, many prior studies have compared end-systolic volume and EDV from echocardiographic volume analysis obtained by a backscatter SEPTEMBER 15, 1997
technique8,10,11 with external standards without further calibration. However, our goal was not to test the validity of geometric-based estimates of echo volumes per se, but to examine the dynamic course of the volume data. Accurate LV volume calculation from 2-dimensional echocardiography relies on accurate apical views,26 and these views were more difficult to obtain in a patient undergoing cardiac catheterization so that LV volume underestimation was anticipated. However, relative area change (and thus volume change) derived from the slightly off-axis apical views that we could obtain should have been comparable to that of the true apical views, supporting our analytic approach. Only one prior study has examined LV volume dynamics, comparing echocardiographic with ultrafast computed tomography data.11 These records were not simultaneous, but were obtained within 5 minutes of each other, and manual tracing was required for computerized tomographic data analysis. The investigators reported a fairly constant negative bias during diastole and early systole and a positive bias during mid to late systole for on-line data relative to corresponding computerized tomographic values. In our study, we did not observe either systematic under- or overestimation of DEQ LV volumes during the cardiac cycle. Although this is mainly due to the calibration procedure for the DEQ data, the calibration should not have influenced systematic phasic errors of the volume data during the cycle. There are several limitations that should be considered. First, although the conductance signal has been validated against a variety of methods,15,27 it is certainly subject to its own errors. However, no other method provides a real-time continuous signal, making it the best available technique for simultaneous DEQ comparisons during steady state and transient volume changes. Second, the DEQ method critically depends on image quality, and this was compromised by having the patient required to lie supine on the catheterization table. While helped somewhat by the tilt table, this flat position was still maintained. Thus, we anticipate that better DEQ volume signals may be obtainable during routine echocardiographic studies. We conclude that the automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans. Acknowledgment: We wish to thank Zadok Nevo, DSc, MD, who designed and built the tilting table for the echocardiographic studies performed in the cardiac catheterization laboratory. We also thank Vingmed for graciously loaning the echocardiographic equipment used in this study.
1. Gorcsan J III, Romand JA, Mandarino WA, Deneault LG, Pinsky MR. Assessment of left ventricular performance by on-line pressure-area relations using echocardiographic automated border detection. J Am Coll Cardiol 1994; 23:242–252. 2. Sharir T, Feldman MD, Haber H, Feldman AM, Marmor A, Becker LC, Kass DA. Ventricular systolic assessment in patients with dilated cardiomyopathy by
preload-adjusted maximal power. Validation and noninvasive application. Circulation 1994;89:2045–2053. 3. Gorcsan J III, Lazar JM, Romand J, Pinsky MR. On-line estimation of stroke volume by means of echocardiographic automated border detection in the canine left ventricle. Am Heart J 1993;125:1316 –1323. 4. Gorcsan J III, Gasior TA, Mandarino WA, Deneault LG, Hattler BG, Pinsky MR. On-line estimation of changes in left ventricular stroke volume by transesophageal echocardiographic automated border detection in patients undergoing coronary artery bypass grafting. Am J Cardiol 1993;72:721–727. 5. Tardif JC, Cao QL, Pandian NG, Esakof DD, Pollard H. Determination of cardiac output using acoustic quantification in critically ill patients. Am J Cardiol 1994;74:810 – 813. 6. Lindower PD, Rath L, Preslar J, Burns TL, Rezai K, Vandenberg BF. Quantification of left ventricular function with an automated border detection system and comparison with radionuclide ventriculography. Am J Cardiol 1994;73:195–199. 7. Gorcsan J III, Lazar JM, Schulman DS, Follansbee WP. Comparison of left ventricular function by echocardiographic automated border detection and by radionuclide ejection fraction. Am J Cardiol 1993;72:810 – 815. 8. Vanoverschelde JLJ, Hanet C, Wijns W, Detry JM. On-line quantification of left ventricular volumes and ejection fraction by automated backscatter imagingassisted boundary detection: comparison with contrast cineventriculography. Am J Cardiol 1994;74:633– 634. 9. Yvorchuk KJ, Davies RA, Chan KL. Measurement of left ventricular ejection fraction by acoustic quantification and comparison with radionuclide angiography. Am J Cardiol 1994;74:1052–1056. 10. Gorcsan J III, Morita S, Mandarino WA, Deneault LG, Kawai A, Kormos RL, Griffith BP, Pinsky MR. Two-dimensional echocardiographic automated border detection accurately reflects changes in left ventricular volume. J Am Soc Echocardiogr 1993;6:482– 489. 11. Marcus RH, Bednarz J, Coulden R, Shroff S, Lipton M, Lang RM. Ultrasonic backscatter system for automated on-line endocardial boundary detection: evaluation by ultrafast computed tomography [see comments]. J Am Coll Cardiol 1993;22:839 – 847. 12. Jiang L, Morrissey R, Handschumacher MD, Vazquez de Prada JA, He J, Picard MH, Weyman AE, Levine RA. Quantitative three-dimensional reconstruction of left ventricular volume with complete borders detected by acoustic quantification underestimates volume. Am Heart J 1996;131:553–559. 13. Feldman MD, Pak PH, Wu CC, Haber HL, Heesch CM, Bergin JD, Powers ER, Cowart TD, Johnson W, Feldman AM, Kass DA. Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure. Circulation 1996;93:474 – 483. 14. Senzaki H, Chen CH, Kass DA. Single-beat estimation of end-systolic pressure-volume relation in humans. A new method with the potential for noninvasive application. Circulation 1996;94:2497–2506. 15. Kass DA, Yamazaki T, Burkhoff D, Maughan WL, Sagawa K. Determination of left ventricular end-systolic pressure-volume relationships by the conductance (volume) catheter technique. Circulation 1986;73:586 –595. 16. Glower DD, Spratt JA, Snow ND, Kabas JS, Davis JW, Olsen CO, Tyson GS, Sabiston DC, Rankin JS. Linearity of the Frank-Starling relationship in the intact heart: the concept of preload recruitable stroke work. Circulation 1985;71:994–1009. 17. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–312. 18. Hultman J, Palmgren I, Landelius J, Andren B. Transoesophageal echocardiography and acoustic quantification in assessing regional left ventricular wall motion. Acta Anaesth Scand 1994;38:575–579. 19. Perez JE, Klein SC, Prater DM, Fraser CE, Cardona H, Waggoner AD, Holland MR, Miller JG, Sobel BE. Automated, on-line quantification of left ventricular dimensions and function by echocardiography with backscatter imaging and lateral gain compensation. Am J Cardiol 1992;70:1200 –1205. 20. Kolev N, Huemer G, Steiner W, Leitner K. On-line assessment of left ventricular volumes and ejection fraction by automatic boundary detection and ultrasonic backscatter imaging. J Cardiovasc Diagn Proc 1996;11:141–145. 21. Vandenberg BF, Rath LS, Stuhlmuller P, Melton HE Jr, Skorton DJ. Estimation of left ventricular cavity area with an on-line, semiautomated echocardiographic edge detection system. Circulation 1992;86:159 –166. 22. Perez JE, Waggoner AD, Barzilai B, Melton HE Jr, Miller JG, Sobel BE. On-line assessment of ventricular function by automatic boundary detection and ultrasonic backscatter imaging. J Am Coll Cardiol 1992;19:313–320. 23. Stoddard MF, Keedy DL, Longaker RA. Two-dimensional transesophageal echocardiographic characterization of ventricular filling in real time by acoustic quantification: comparison with pulsed Doppler echocardiography. J Am Soc Echocardiogr 1994;7:116 –131. 24. Chenzbraun A, Pinto FJ, Popylisen S, Schnittger I, Popp RL. Filling patterns in left ventricular hypertrophy: a combined acoustic quantification and Doppler study. J Am Coll Cardiol 1994;23:1179 –1185. 25. Chenzbraun A, Pinto FJ, Popylisen S, Schnittger I, Popp RL. Doppler echocardiography in assessment of left ventricular diastolic variables. Br Heart J 1993;70:448 – 456. 26. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux RB, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik AJ. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989;2:358 –367. 27. Lankford EB, Kass DA, Maughan WL, Shoukas AA. Does volume catheter parallel conductance vary during a cardiac cycle? Am J Physiol 1990;258: H1933–H1942.
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MD,
and
Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 6 15 years, range 22 to 70; ejection fraction 63 6 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter 5 slope z DEQ 1 intercept, slope 5 0.94 6 0.09, inter-
cept 5 5 6 8 ml, r2 5 0.86 6 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 6 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. Enddiastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 6 0.31, mean intercept 14 6 37 ml, average r2 5 0.89 6 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 6 0.43, intercept 5 220 6 26 ml, r2 5 0.67 6 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans. Q1997 by Excerpta Medica, Inc. (Am J Cardiol 1997;80:756 –761)
R
angiography,8 ultrafast computed tomography,11 thermodilution,5 3-dimensional reconstructions,12 and simultaneous aortic flow measurements.4 The only study evaluating the dynamics of the LV volume signal compared short-axis area curves during a steady-state cycle with those measured by nonsimultaneous ultrafast computed tomography,11 and reported systematic errors in estimating end-systolic and end-diastolic areas. To date, echocardiographic continuous LV volumes derived by conventional transthoracic approaches at steady state and during loading transients have not been validated against simultaneously measured LV volumes in humans. The present study was designed to test this by comparing a new transthoracic digital echo quantification method with volumes measured by intracardiac conductance catheter.
eal-time, continuous left ventricular (LV) volume can be estimated by an echocardiographic backscatter technique that detects the endocardial border and calculates the left ventricular area automatically. Such volume data are useful for determining cardiac performance parameters such as ejection fraction, pressure-volume relations,1 and maximal power indexes.2 The accuracy of steady-state stroke volume,3,4 cardiac output,5 ejection fraction,6 –9 and end-systolic and end-diastolic volumes8,10,11 determined by this technique have been evaluated by comparisons with nonsimultaneous radionuclide imaging,9 contrast LV From the Division of Cardiology, Department of Internal Medicine, Johns Hopkins University Medical Institutions, Baltimore, Maryland. Dr. Chen-Huan Chen is a Clinical Research Fellow from the Division of Cardiology, Department of Medicine, Veterans General HospitalTaipei and National Yang-Ming University, Taipei, Republic of China. This study was supported by NIA Grant AG:12249 (D.A.K.), Bethesda, Maryland; Colin Research Fellowship Award (B.F.), San Antonio, Texas; and a Fogarty Foundation Grant (E.N.)., Bethesda, Maryland. Manuscript received March 6, 1997; revised manuscript received and accepted May 21, 1997. Address for reprints: David A. Kass, MD, Halsted 500, Division of Cardiology, The Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, Maryland 21287.
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©1997 by Excerpta Medica, Inc. All rights reserved.
METHODS
Study subjects: Nineteen patients underwent 21 diagnostic pressure-volume loop catheterizations (2 patients underwent separate catheterizations 1 year apart). Echocardiographic images were of insufficient quality for analysis in 3 patients, and these data were 0002-9149/97/$17.00 PII S0002-9149(97)00509-2
FIGURE 1. A sample echocardiogram showing apical 4-chamber view endocardial delineation by DEQ. The region of interest is manually drawn around the left ventricle. Real-time, continuous left ventricular (LV) volume (VOL) curve is displayed in the lower panel, along with the electrocardiogram (ECG) and calculated variables, which are given as numerical values and are updated each cycle. EDV 5 end-diastolic volume; ESV 5 end-systolic volume; EF 5 ejection fraction; HR 5 heart rate; SV 5 stroke volume.
not used. Mean age of the remaining 16 patients (9 men, 7 women) was 50 6 15 years (range 22 to 70). Clinical diagnosis included coronary artery disease (2 patients), hypertensive cardiovascular disease (1 patient), hypertrophic obstructive cardiomyopathy (1 patient), dilated cardiomyopathy (1 patient), constrictive pericarditis (1 patient), and post-heart transplantation (10 patients). Ejection fraction ranged from 15% to 85% (mean 63 6 20%). Informed consent approved by the Joint Committee on Clinical Investigation was obtained from each patient. Digital echo quantification method: The digital echo quantification (DEQ, Vingmed Sound, Norway) used in this study processes raw high-quality 2-dimensional images in a 4-chamber longitudinal view, with fine gray-scale resolution obtained by a 12-bit A/D converter. Raw backscatter data are digitized, stored to memory, and subject to a dynamic processing algorithm that applies temporal and spacial digital filtering and statistically based edge-detection enhancement. A contour identifying the myocardial blood pool interface is superimposed on the real-time echocardiographic image and used for automated area calculation. Areas are transformed to volumes by combining with the ventricular long axis, which is assumed to be constant during contraction. Calculated area or volumes are displayed as a real-time trace (Figure 1), and exported as an analog signal. Procedures: In several patients, the echo image quality was severely limited due to the need for the patient to lie supine on the catheterization table. Therefore, a custom-designed radio-transparent lightweight tilting table was used. The operator could tilt the patient from 0 to 30° toward a left lateral decubitus position to enhance echocardiographic image quality. After routine coronary angiography, left ventriculog-
raphy, and right heart catheterization, a 7Fr multielectrode pressure-conductance volume catheter (SSD-767 or 768, Millar Instruments, Houston, Texas) was introduced via a femoral artery, advanced to the LV apex, and connected to stimulator microprocessor (Sigma V, CardioDynamics, Bijnsdurg, the Netherlands) to generate a volume signal.13 During acquisition of invasive pressure-volume data, echocardiographic images and DEQ processing were simultaneously obtained (model CFM 800, Vingmed Sound) using a 3.2- or 2.5MHz mechanical sector transducer. Data were acquired in standard apical 4-chamber view so the detected LV area could be directly converted to LV volume by the single-plane area-length method. Invasive high-fidelity LV pressure and volume signals from the conductance catheter, and the noninvasive LV volume derived from the DEQ analysis of the echo image were digitized simultaneously at 200 or 250 Hz, both at steady state and during preload reduction. The latter was achieved by transient intraluminal obstruction of inferior vena cava flow by balloon catheter (SP:9168, Cordis, Miami, Florida). Data analysis: Digitized hemodynamic data were analyzed off-line using custom software developed under the environment of MATLAB for Windows, version 4.2c (The MathWorks Inc). Both volume signals were digitally filtered (8 order, zero phase, Butterworth filters with a 20-Hz cutoff) to reduce noise. Respiration significantly effected transthoracic 2-dimensional echocardiographic images, and thus the DEQ volume signals showed clear respiratory variation. Signal averaging over at least 1 respiratory cycle removed this variability from steady-state data. For DEQ volume data during preload reduction, a fastFourier transformation band-stop filter was applied with cutoff frequencies (ranges 0.3 to 0.5 Hz) determined for each patient based on individual frequency of respiration. Both noninvasive and invasive volume signals were calibrated by matching the average width of the pressure-volume loop to stroke volume calculated by dividing thermodilution-derived cardiac output by heart rate.13,14 By further matching ejection fraction to that measured by contrast ventriculography, absolute calibration was achieved. The DEQ processing for calculation of echocardiographic area and volume introduced a time delay into the analog volume signal,1,11 compared with the instantaneous invasive signal derived from the conductance catheter. To adjust for this delay, which varied among patients, the 2 volume signals were aligned by matching the minimum and maximum volume time points. Catheter and DEQ-based volume signals from 10 to 15 consecutive heart cycles were averaged, and maximum and minimum points identified from the respective signal-averaged cycles. The times from the R wave of the electrocardiogram to each of these fiduciary volume-signal time points were averaged for each averaged cycle, and the difference in this averaged time was used as a measure of the delay of the METHODS/VALIDATION OF DEQ VOLUME
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volumes from the catheter and DEQ volumes were compared by linear regression analysis. To further test the clinical usefulness of the DEQ volume pressure-volume data, several variables were calculated from steady-state pressure-volume loops and from the preload-reduction pressurevolume relations. Steady-state parameters included: LV end-diastolic pressure, measured as the pressure at the right lower corner of the pressure-volume loop, peak filling rate (PFR) normalized by EDV (PFR/EDV), equal to the first derivative of the volume curve divided by EDV, and external stroke work, equal to the area within the pressure-volume loop. Parameters derived from the preload reduction data included end-systolic pressure-volume relation,15 volume intercept at zero pressure,15 and preload recruitable stroke work.16 Statistical analysis: Comparison between DEQ and conductance catheter volumes were analyzed by linear regression. Bland-Altman analysis17 was used to examine the agreement of various indexes derived from DEQ and volume catheter data, and the paired Student’s t test was used to test the mean differences.
RESULTS
Comparison of catheter and DEQ volumes at steady state: There was greater
beat-to-beat variability of the DEQ volume trace than of the catheter volume signal, demonstrated in the volumetime curves (Figure 2A) and mean 6 SD envelopes for signal-averaged volume data (Figure 2B, right panel). However, signal-averaged DEQ volume curves tracked the catheter volume curves well during an averaged cardiac cycle (Figure 2B, left panel). Maximal positive differences between DEQ and catheter volumes (Figure 2C) ranged from 6 to 27 ml (mean 16 6 8), and maximal negative differences from 238 to 24 ml (mean 214 6 9). Regression analysis between catheter and DEQ volume (Figure 2C, right panel) yielded a mean slope of 0.94 6 0.09, intercept 5 6 8 ml, and r2 5 0.86 6 0.12.
FIGURE 2. An example of the measured and analyzed data from 1 patient during steady state. A, simultaneously recorded catheter and DEQ left ventricular volumes; B (left panel), signal-averaged catheter (dotted line) and DEQ (solid line) volumes for 1 cardiac cycle; right panel, mean 1 SD and mean 2 SD boundaries for the signal-averaged catheter (dotted lines) and DEQ (solid lines) volumes. The boundaries are wider for the DEQ volume; C (left panel), point-by-point difference (solid line) and its 6 1 SD boundaries (dashed lines) of the signal-averaged catheter and DEQ volumes. Solid arrow indicates timing of maximum difference and hollow arrow indicates timing of minimum difference; right panel, linear regression analysis for the 2 signal-averaged volumes.
DEQ signal. The original DEQ data were then phaseadvanced by this amount. For steady-state recordings, the phase aligned volume signals from 10 to 15 consecutive heart cycles were averaged to generate a comparison cycle. Time courses of the averaged catheter and DEQ volume signals from each patient were compared directly by computing point-to-point difference and linear regression. To summarize the comparison for the overall study population, signal-averaged catheter and DEQ volume traces from each patient were resampled to provide 100 data points with equal spacing. The resampled catheter and DEQ volume traces were then group averaged. For recordings during inferior vena caval occlusion, end-diastolic (EDV) and end-systolic 758
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Comparison of catheter and DEQ volumes during inferior vena caval occlusion: Echo images degraded
during inferior vena caval occlusion in half of the studies due to a change in cardiac position relative to the echo probe, or to respiratory chest wall movement. Analyzable recordings of DEQ volume during inferior vena caval occlusion were obtained in the remaining 9 studies. Inferior vena caval occlusion yielded a 45 6 SEPTEMBER 15, 1997
FIGURE 3. An example of the measured and analyzed data from 1 patient during inferior vena caval obstruction. A, simultaneously recorded catheter and DEQ left ventricular volumes; B, linear regression analysis for end-diastolic volume (EDV); C, linear regression analysis for end-systolic volume (ESV); D, linear regression analysis for whole tracings.
FIGURE 4. A, an example showing steady-state pressure volume loop constructed from signal-averaged invasive left ventricular (LV) pressure and catheter (dotted line) or noninvasive DEQ (solid line) volume; B to D, Bland-Altman analysis for end-diastolic pressure (EDP) (B), peak filling rate/end-diastolic volume (PFR/EDV) (C), and external stroke work (SW) (D) calculated from the steady-state signal-averaged catheter and DEQ volumes and/or LV pressure. Dashed lines indicate mean differences; dotted lines, boundaries of 2 SDs of the differences.
13% decrease in EDV. Beat-by-beat EDV changes determined by the 2 volume methods were significantly correlated (mean slope 0.88 6 0.31, mean intercept 14 6 37 ml, average r2 5 0.89 6 0.11, each individual r2 value had a p value ,0.01) (Figure 3).
For end-systolic volumes, results were significant but displayed more scatter, with a mean slope of 0.80 6 0.43, intercept 5 220 6 26 ml, and r2 5 0.67 6 0.18, all p ,0.05. Figure 3D displays simultaneous volumevolume data for the transient data displayed in panel METHODS/VALIDATION OF DEQ VOLUME
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FIGURE 5. A and B, same sample from Figure 4 showing pressure–volume loops constructed from invasive left ventricular pressure and catheter (A) or noninvasive DEQ (B) volume. Although there were good correlations for the end-systolic/end-diastolic volumes of the volume signals, the loop shapes were not similar. Dotted lines indicate end-systolic pressure-volume relation (Ees) slope from the catheter volume; solid line, Ees slope from the DEQ volume. C and D, linear regression analysis for the Ees (C), volume intercept at zero pressure (V0) (D), and preload recruitable stroke work (PRSW) (E) calculated from left ventricular pressure and catheter or DEQ volumes during preload reduction.
A, revealing reasonable correlation throughout but wider scatter around the regression line. Hemodynamic variables derived from DEQ volume and pressure-volume data: Results of steady-state and
transient pressure-volume and volume signal analysis are shown in Figures 4 and 5. Figure 4A displays example steady-state pressure-volume loops constructed from catheter and DEQ volumes, respectively. Correlations between variables from steadystate pressure volume loops were good (Figure 4B to 4D), with no consistent bias in the estimate by DEQ method, and most of the differences falling within an acceptable range. Figure 5A to 5B shows example pressure-volume data during inferior vena caval obstruction. Conversely, there were only fair correlations for indexes derived from the preload transient data (Figure 5C to 5E).
DISCUSSION Continuous echocardiographic LV volume signals were first made available by using a backscatter technique, and have been applied to the evaluation of LV systolic1,3–10,18 –22 and diastolic function.23–25 However, this echocardiographic-derived LV volume sig760
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nal has never been directly compared with simultaneously obtained independent continuous LV volumes either at steady state or during transient changes in cardiac volume. This study performed such comparisons between a new method for real-time, continuous LV volume echo-based signal analysis (DEQ) and data measured by invasive conductance catheter. The 2 volume signals were generally well correlated, and the data could be used to construct steady-state pressure-volume loops and assess a number of useful hemodynamic indexes. However, stable DEQ images were definitely more difficult to maintain during loading transients. Whereas DEQ end-systolic and enddiastolic volumes correlated reasonably well with catheter volumes in the studies with persistent images, the derived hemodynamic indexes were less reliable. In this study, the DEQ signal was itself precalibrated by the same external standards (i.e., thermodilution cardiac output and ventriculographic ejection fraction) used to calibrate the conductance catheter signal. In contrast, many prior studies have compared end-systolic volume and EDV from echocardiographic volume analysis obtained by a backscatter SEPTEMBER 15, 1997
technique8,10,11 with external standards without further calibration. However, our goal was not to test the validity of geometric-based estimates of echo volumes per se, but to examine the dynamic course of the volume data. Accurate LV volume calculation from 2-dimensional echocardiography relies on accurate apical views,26 and these views were more difficult to obtain in a patient undergoing cardiac catheterization so that LV volume underestimation was anticipated. However, relative area change (and thus volume change) derived from the slightly off-axis apical views that we could obtain should have been comparable to that of the true apical views, supporting our analytic approach. Only one prior study has examined LV volume dynamics, comparing echocardiographic with ultrafast computed tomography data.11 These records were not simultaneous, but were obtained within 5 minutes of each other, and manual tracing was required for computerized tomographic data analysis. The investigators reported a fairly constant negative bias during diastole and early systole and a positive bias during mid to late systole for on-line data relative to corresponding computerized tomographic values. In our study, we did not observe either systematic under- or overestimation of DEQ LV volumes during the cardiac cycle. Although this is mainly due to the calibration procedure for the DEQ data, the calibration should not have influenced systematic phasic errors of the volume data during the cycle. There are several limitations that should be considered. First, although the conductance signal has been validated against a variety of methods,15,27 it is certainly subject to its own errors. However, no other method provides a real-time continuous signal, making it the best available technique for simultaneous DEQ comparisons during steady state and transient volume changes. Second, the DEQ method critically depends on image quality, and this was compromised by having the patient required to lie supine on the catheterization table. While helped somewhat by the tilt table, this flat position was still maintained. Thus, we anticipate that better DEQ volume signals may be obtainable during routine echocardiographic studies. We conclude that the automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans. Acknowledgment: We wish to thank Zadok Nevo, DSc, MD, who designed and built the tilting table for the echocardiographic studies performed in the cardiac catheterization laboratory. We also thank Vingmed for graciously loaning the echocardiographic equipment used in this study.
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