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Measurement of ejection fraction by thermal dilution techniques
JOURNAL
OF SURGICAL
Measurement
RESEARCH
34,
331-346 (1983)
of Ejection Fraction by Thermal Dilution Techniques’
HAROLD R. KAY, M.D., *** MANOUCHERAFSHARI, M.D.,* PAUL BARASH,M.D.,? WILLIAM WEBLER, B.S.M.E.,$ ABDULMASSIH ISRANDRIAN,
M.D.,5
CHARLESBEMIS, M.D.,5 A-HADI HAKKI, M.D.,* AND ELDREDD. MUNDTH, M.D.* *Department of Cardiothoracic Surgery and $Section of Cardiology, Hahnemann University, Philadelphia, Pennsylvania 19102, and the VDepartment of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06520, and *American Edwards Laboratories, Santa Ana, California 92711 Presented at the Annual Meeting of the Association for Academic Surgery, San Diego, California, November 7-10, 1982 The reproducibility, accuracy, and clinical applicability of ventricular ejection fraction derived by a thermal dilution technique were assessed in 22 dogs and 18 patients. Results obtained by the thermal technique were compared to simultaneous results obtained by radionuclide angiography. Right ventricular ejection fraction, measured in 9 dogs (1014 determinations) and 8 patients (744 determinations) was reproducible +5%. Left ventricular ejection fraction, measured in 10 patients, was reproducible f5W. Correlation between thermal and radionuclear measurements varied from 0.86 to 0.93 (all P < 0.02). We conclude that, because of its low cost, ease of use, and accuracy, thermally derived ejection fraction determinations can be helpful in hemodynamic monitoring of critically ill patients.
INTRODUCTION
Precise measurement of ejection fraction has potential prognostic [ 181,diagnostic, and therapeutic [ 12, 131advantages. However, logistic constraints imposed by existing techniques preclude routine measurement of these indices in critically ill patients. The three currently available methods (radionuclear angiography, contrast angiography, and echocardiography) all require large, expensive imaging systems and special personnel which make it difficult to accurately monitor ejection fraction at the bedside. In addition, the risk to the patient from accumulated radiation or from repetitive angiographic dye injections make it difficult to perform serial measurements. Knowledge of ejection fraction may be critical in pre- and postoperative care of patients with poor ventricular function in whom early recognition of impending ventricular dysfunction might allow earlier, more effective ’ Supported in part by a grant from American Edwards laboratories, Santa Ana, California. * To whom requests for reprints should be sent at Department of Cardiothoracic Surgery, Hahnemann University, 230 North Broad St., Philadelphia, Penn. 19102. 337
intervention. In addition, becauseventricular compliance can change rapidly in the compromised ventricle [ 121, therapy directed at “optimization” of filling pressures may not improve ventricular performance [5]. The principle of using indicator solutions to measure residual volume (the volume of blood remaining in the ventricle during isometric relaxation) was described by Holt [8] and confirmed by Salgado [ 161.Bing [3] has discussed the principles of right ventricular residual volume measurement. Unfortunately, early investigations with the use of an iced saline bolus as an indicator solution were frustrated by inadequate technology; the response time of the thermistor was only 300 msec. Although this response time is adequate for calculation of cardiac output, it is too slow for calculation of ventricular volumes. Currently available mounted thermistors have an average response time of only 1000 msec [l]. A recent technological advance has allowed manufacture of mounted thermistors with a responsetime of 50 msec. This rapid response thermistor is fast enough to measure beatto-beat temperature variations and allows 0022-4804/83 $1 SO Copyright 0 1983 by Academic Press. Inc. All rights of reproduction in any form reserved.
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JOURNAL OF SURGICAL RESEARCH: VOL. 34, NO. 4, APRIL 1983
FIG. 1. Position and configuration of the modified Swan-Ganz catheter in either the canine or human
calculation of ventricular volumes (see Appendix). This study was designed to evaluate the reproducibility, accuracy, and clinical applicability of the thermal technique to calculate ejection fraction in both the right and left ventricles. MATERIALS
AND
METHODS
The study was conducted using both animal and human subjects. Preliminary investigations regarding modeling technique, computer algorithms, and optimum injectate temperature and volume were assessedin a canine right ventricle model (CANINE RIGHT VENTRICLE). Subsequent human investigations were conducted either in patients undergoing cardiac operations (HUMAN RIGHT VENTRICLE) or cardiac catheterization (HUMAN LEFT VENTRICLE). Informed consent was obtained for all human
studies under a protocol approved by the Human Studies Committee. Canine Right Ventricle Twenty-two mongrel dogs were anesthetized using pentobarbitol, intubated and ventilated with a volume-limited respirator. A 7F Swan-GanzB3catheter, modified with a rapid response thermistor, and manufactured with dimensions appropriate for a dog, was positioned into the pulmonary artery via a percutaneous jugular venous cutdown (Fig. 1). In addition to the right ventricular and pulmonary artery pressures(recorded through the various ports of the Swan-Ganz@ catheter), femoral artery pressureand pulmonary artery temperature were continuously monitored and stored on a physiologic tape recorder. An American Edwards Model 9310 Lung 3 %wan-Ganz is a registered trademark of American Edwards Laboratories.
KAY ET AL.: THERMAL
Water Computer was modified using a preprogrammed computer microchip to allow amplification of the thermistor output signal (pulmonary artery temperature) and calculation of cardiac output. Ejection fraction was calculated using the formulas in Figs. 2 and 3 (see Appendix), Continuous intravenous isoproterenol and volume loading were used to increase right ventricular ejection fraction (RVEF) from 3540% (normal RVEF) to 55-70% (high RVEF). These agents also increased heart rate and cardiac output. Ejection fraction was decreased to 17-30% (low RVEF) by increasing right ventricular afterload (intravenous neosynephrine or respiratory acidosis). At all three levels of ejection fraction (normal, high, and low) injectate site (right atrium or right ventricle), volume (3, 5, or 10 ml), and temperature (4 or 24°C) were randomly varied. Multigated equilibrium blood pool imaging was performed using in vivo labeling of red blood cells with unlabeled stannous pyrophosphate before injecting 12-l 5 mc of technetium-99m or sodium pertechnetate. The dogs were positioned in the lateral projection, and the camera in 30” LAO projection with lo- 15’ caudal angulation. This was the best projection to separate the right ventricle and the left ventricle. Collection of data was performed with a standard gamma scintillation camera (series 420 Mobile Gamma
RF = Mean
Residual
Fraction
0.5oc I
FIG. 2. A typical thermal washout curve. The thermal bolus is injected immediately after the 0S”C standard. The plateaus on the downslope portion of the curve rep resent diastole when there is little flow and therefore little change in temperature. C, , C,, and C, represent the differencesin temperature between baseline and the respective diastoles. Note a decreasein temperatures is an upward deflection of the curve.
339
EJECTION FRACTION sv = COIHR CO = k,SrSS under the thermal EDV = SVlEF ESV = EDV _ ESV Where Sv = Stroke Volume co = csrdisc output k = A Constant EDV = End Diastolic Volu”%* EF = Ejection Friction ESV = End Systolic Volume
washout
Curve
FIG. 3. Formulas to obtain stroke volume, cardiac output, end-diastolic volume, and end-systolic volume from the thermal washout curve.
Camera, Technicare) equipped with a low energy all-purpose collimater. The image data were acquired with a dedicated nuclear medicine minicomputer (VIP 550, Technicare) and formatted into a 64 X 65 matrix. A mean R-R interval was determined by averaging five beats immediately prior to data acquisition and data were divided into 16 equal frames. Cardiac cycles with R-R intervals greater than 20% of the mean R-R interval were rejected. A total of 250,000 counts/frame were accumulated in the whole field of view. The energy window (20%) of the gamma camera was set symmetrically around the 140 keV photo peak. Regions of interest were drawn over the right ventricle by visual inspection taking care to include the entire right ventricle while excluding as much of the right atrium and pulmonary artery as possible. The end-diastolic and end-systolic frames were identified and smoothed with a nine point centerweighted filter. Background correction was performed by a linear interpolated subtraction technique. Separate right ventricular regions of interest were constructed for the end-diastolic and end-systolic frames. The frames were displayed in endless loop movie format to assist in identification of ventricular borders. The right ventricular ejection fraction was calculated r+ end-diastolic counts - end-systolic counts end-diastolic counts x 100. Human Right Ventricular Studies
Eight patients scheduled to undergo elective cardiac operations were used to evaluate
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the reproducibility and accuracy of serial determinations of ejection fraction during the perioperative period. Prior to induction of anesthesia a SwanGanz@ catheter, modified with a rapid response thermistor, was positioned into the pulmonary artery (Fig. 1). The operation then proceeded in the routine fashion, At various times during the operation right ventricular ejection fraction was determined. At the conclusion of the operation patients were transferred to the intensive care unit and ejection fraction was calculated whenever a determination of cardiac output was clinically indicated. No pharmacologic manipulations were carried out except as clinically indicated. On the third postoperative day a first-pass radionuclide angiogram was done and left and right ventricular ejection fraction and cardiac output were calculated. Thermal ejection fraction, cardiac output, and ventricular volumes were measured simultaneously. lnjectate volume (5 or 10 ml), site (right atrium or right ventricle) and temperature (4 or 24°C) were varied to assessthe accuracy of ejection fraction as a function of differing injectate parameters. All thermal measurements were done in duplicate or triplicate and the results averaged. Human Left Ventricular Studies Ten patients undergoing elective cardiac catheterization for a variety of indications participated in the study. A 3F probe with a rapid response thermistor was inserted percutaneously into the femoral artery and positioned in the ascending aorta. A separate catheter was positioned into the left atrium (via a patent foramen ovale or retrograde across the mitral valve) or retrograde across the aortic valve into the left ventricle. Left ventricular ejection fraction and volumes were calculated following either ( 1) a 10 ml saline bolus into either the left atrium or left ventricle, or (2) injection of angiographic dye into the left ventricle (routine ventriculogram). A first-pass radionuclide angiogram was
performed in all patients at the conclusion of the cardiac catheterization. Left ventricular volumes were calculated by radionuclide, thermal, and contrast angiographic techniques. The results of these three techniques were compared. In human subjects the right and left ventricular ejection fractions were determined in the anterior projection by the first-passmethod using a computerized multicrystal camera (Baird-Atomic Systems-77, Bedford, Mass.). The ejection fraction was determined from the background corrected cardiac cycle as end-diastolic counts - end-systolic counts end-diastolic counts x 100. The method has previously been described by this and other laboratories [2, 10, 171. Data Analysis Reproducibility of calculations was determined by comparing consecutive determinations under steady state conditions. Accuracy of thermal-derived values was assessed by comparison to simultaneously derived radionuclide or angiographic values. Comparison between consecutive measurements (reproducibility) or between different thermal and nuclear measurements (accuracy) was determined using analysis of variance, paired t test, correlation coefficient analysis, and linear regressiontechniques. All data is expressedas mean f standard error and a P value of co.05 was considered significant. RESULTS
Canine Right Ventricle Figure 4 graphs the results of 329 pairs of consecutive ejection fraction determinations following a saline bolus into the right atrium. The determinations were done under steady stateconditions (normal, high, or low ejection fraction) using different injectate temperatures (4 or 24°C) and volumes (3, 5, or 10 ml). Figure 5 graphs the results following saline injections into the right ventricle.
KAY
ET AL.: THERMAL
The results after right ventricular injections are less reproducible than the results after right atria1 injections which is probably a function of inadequate mixing during right ventricular injections [ 191. When the RA and RV injection data are pooled, the 70% confidence limit is 6%, implying that consecutive determinations are reproducible f6%. Injectate volume and temperature had no significant effect on measured ejection fraction. Figure 6 shows the comparison between ejection fraction simultaneously measured by thermal and multigated blood pool imaging techniques. Although the correlation is reasonable, (I = 0.9) and significant (P < 0.01) the regression equation is
Y = 0.92(X) + 18. The high intercept value of 18 suggests that either the gated technique consistently underestimates ejection fraction or the thermal technique consistently overestimates ejection fraction. However, the slope of the equation (0.92) implies that, once the 18% effect is taken into consideration, increases or decreases in ejection fraction are accurately reflected by either technique.
Human Right Ventricle
EJECTION
FRACTION
RVEFSECOND INJECTION
341
40.
FIG. 5. Comparison between consecutive thermal ejection fractions in the canine right ventricle following a thermal bolus into the right ventricle.
crepancy is accentuated in patients with low ejection fractions (~25%). When ejection fraction is >30% the data points are in closer alignment. When consecutive thermal determinations (372 pairs) of ejection fraction are compared under steady state conditions, the reproducibility of the determination (70% confidence limit) is +-5%. As in the dog model, right atria1 injections are more reproducible than right ventricular injections and injectate volume (5 or 10 ml) and temperature (4 or 24°C) have no significant effect on the measurement.
Human Left Ventricle
Figure 7 graphs the results of a comparison of simultaneously measured thermal and firstpass studies in 10 patients. Examination of individual data points shows again that the nuclear determination is lower than the thermal values and the dis-
RVEF40. SECOND INJECTIONM. w x). r = 0.80 P
FIG. 4. Comparison between consecutive ejection fractions in the canine right ventricle following a thermal bolus into the right atrium.
Figure 8 shows the comparison between first-pass and thermal measurements in the human left ventricle. The data compares 19 thermal determinations in 10 patients. Nuclear ejection fraction was measured only once in each patient. Ten thermal data points represent the results following a saline injection into the left atrium. The additional 9 thermal data points represent the measured ejection fraction following a 30-40 ml room temperature injection of angiographic dye into the left ventricle. The highly significant correlation coefficient (r = 0.93, P < 0.00 1) and virtual identity of the linear regression line substantiate the accuracy of thermally derived left ventricular ejection fraction. Injectate site (left atrium or ventricle), tem-
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60 ‘. 50 THERMAL RVEF (%I
40
I::
40
10
GATED%“CLEAYi)R (%I
RVEF
FIG. 6. Comparison between thermal and gated nuclear determinations of ejection fraction in the canine right ventricle.
perature (4 or 24”C), and composition (saline or angiographic dye) had no significant effect on calculation of ejection fraction. A total of 342 determinations of ejection fraction were calculated in the 10 patients. The calculated ejection fraction was reproducible +5% (70% confidence limit). DISCUSSION
Thermal techniques provide a convenient, inexpensive, safe, and accurate method of measuring cardiac output, ejection fraction, and ventricular volumes. The technique is particularly appealing for serial monitoring of right ventricular function for it is no more invasive than the insertion of a Swan-Ganz@ catheter. Our studies show that repetitive measurements of ejection fraction are reproducible t5% even at extreme ranges of ejection fraction. This reproducibility compares favorably with other techniques. Unfortunately there is no “gold standard” against which to compare thermally derived right ventricular ejection fraction. In our dog studies we compared thermally derived ejection fraction to results obtained from a multigated blood pool imaging technique. However, adequate separation of the right ventricle from left ventricle and adequate definition of right ventricular borders are difficult in the animal model, resulting in contamination with data derived from the right atrium and possibly also cutting off some counts from the region of the outflow tract. We suspect that
this accounts for the discrepancy between the nuclear and thermal values in the animal study. This problem with right ventricle gated images has been described in man [ 15, 171 and may be more pronounced in the dog [6]. Despite the problems inherent in the gated technique, it is encouraging that the correlation coefficient between the two techniques is still good (r = 0.86, P < 0.01) implying that changes in right ventricular ejection fraction are accurate, although the nuclear values are consistently lower. The first-pass technique is less subject to errors in measurement because it is a timephase study in which the isotopic tracer is followed from the great veins through the right atrium, right ventricle, and out into the pulmonary artery. Therefore, by selecting appropriately timed frames, radioactivity can be counted at the precise time that the isotope bolus is in the appropriate (RA, RV, or PA) location. When the thermal and first-pass techniques are compared in the human right ventricle, not only is the correlation good (r = 0.90, P < 0.01) but the slope of the regression line approaches 1 and the offset (Y intercept) of the regression line is virtually zero. We are therefore confident that the thermally derived right ventricular ejection fraction is an accurate measurement. Studies on the left ventricle increase confidence in the thermal technique because the
THERMAL RVEF (W 25. Iy=10 r=o.w p
PASS
d:LEAR w
RVEF
FIG. 7. Comparison between thermal and first-passradionuclear determination of ejection fraction in the human right ventricle.
KAY
ET AL.: THERMAL
accuracy of the first-pass technique in the left ventricle is well established. There is good correlation (r = 0.93, P < 0.001) between thermal and nuclear techniques in the human left ventricle. The accuracy of the thermal determination is supported by the slope (virtually 1) and the offset (virtually 0) of the regression line. The first-pass technique to assessventricular volumes is subject to measurement errors (defining the precise borders of the left ventricle), geometric assumptions, attenuation, or overlap of counts. Both angiographic and echocardiographic techniques are subject also to even greater assumptions about ventricular geometry [4, 7, 93. Since the thermal technique is not encumbered by these constraints, we suspectthat, at least theoretically, the thermal technique is potentially more accurate than the other techniques. Assuming that the thermal technique is both accurate and reproducible, the final consideration is its applicability to patient care. The use of serial right ventricular function monitoring is intrinsically less appealing than is monitoring of left ventricular function because clinicians have always had the concept that the left ventricle is more important. While the left ventricle usually is, there are numerous situations when decreased right ventricular function (secondary to ischemia or pulmonary hypertension) precludes adequate right heart output to a normal left ventricle [ 11, 141.In these situations right ventricular function must be optimized before systemic perfusion improves. In other circumstances monitoring right ventricular performance may be extremely important (such as in patients after mitral valve replacement, especially those with pulmonary hypertension, and in patients with chronic obstructive pulmonary disease, pulmonary embolus, adult respiratory distress syndrome, etc.). If serial monitoring of right ventricular performance were readily available, therapeutic regimens could be titrated against objective measurements of right ventricular parameters. Despite the absence of intrinsic appeal of
EJECTION
FRACTION
343
FIG. 8. Comparison between thermal and first-pass radionuclear determination of ejection fraction in the human leti ventricle.
right ventricular ejection fraction as contrasted with the left ventricle, right ventricular volume determinations are easily performed and require no more invasive technology or risk than the risk to which the patient has already been subjected, namely the risk inherent in the insertion of a Swan-Ganz@catheter and determination of cardiac output. The same saline injection that is routinely used for cardiac output determination could be used to calculate ejection fraction, end-diastolic volume, and end-systolic volume. If right atrial and right ventricular pressures are recorded from the Swan-Ganz@catheter, right ventricular pressure-volume relations can be studied. While this may be hemodynamic overkill, the patient risk factor is not increased and the critically ill patient may potentially benefit by an increased physician awareness of the hemodynamic status. In contrast to right ventricular volume determinations, measurement of left ventricular ejection fraction is intrinsically more appealing and its potential application is more widespread. However, left ventricular ejection fraction monitoring entails a significant risk for the patient. There are two areas in which the thermal left heart ejection fraction technique might find clinical application: the cardiac catheterization laboratory and the monitoring of critically ill patients either after cardiac operation or in the intensive care unit. In the catheterization laboratory, serial or sequential measurements of ejection fraction
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with various interventions could be performed by multiple saline injections, without the risk and inconvenience of multiple contrast angiograms. Our data indicate that LVEF and volumes can be reliably measured. Left ventricular ejection fraction and volumes can also be accurately measured using the renographin-76 as a thermal bolus and thus obviating the need for geometric assumptions in the calculations. The risks of serial measurement of left-sided ventricular volumes are twofold: (1) the risk of left-sided thrombus on the catheter with arterial embolism and (2) the risk of arterial air embolism at the time of the bolus injection. The first risk is minimal in the catheterization laboratory as most patients are anticoagulated during the procedure. The second problem, air embolism, is of greater concern, but is something that is routinely done during coronary arteriography. The problems with clot or air embolus are of greater concern if the technique is used in patients outside the catheterization laboratory. Recently, work has shown that heparincoated catheters may reduce the amount of thrombosis. Although the risk of air embolus has to be considered, many postoperative cardiac surgery units already monitor left atria1 pressure. With extreme caution this left atria1 line could be used for introduction of the saline bolus. The potential benefit of measurement of left ventricular ejection fraction must be weighed against the potential risk. We suspect that the knowledge of ejection fraction and left ventricular distention (increased end-diastolic volume) that could be gained from this technique in patients with borderline left ventricular function may outweigh the risk factor. Two other potential problems exist in any determination of ventricular volumes. The first regards measurement of ejection fraction in patients with an irregular heart rate. All techniques to measure ejection fraction will show beat-to-beat variation as a function of diastolic filling time. We have not studied the
VOL. 34, NO. 4, APRIL
1983
effect of varying diastolic filling time on calculated ejection fraction. However, one patient in our serieswas in atrial fibrillation during part of the study. An analysis of his thermal curves showed a good beat-to-beat correlation between a prolonged diastolic filling time and an increased ejection fraction. Becausethe thermal technique has the potential to measure ejection fraction for 4 or 5 consecutive beats, the average ejection fraction during these 4 or 5 beats could be calculated. Alternatively, the ejection fraction could be calculated for each individual beat, thus deriving a maximum and a minimum ejection fraction. A second problem (or advantage) of the thermal technique regards its applicability in patients with A-V valve regurgitant lesions or intracardiac shunts. By definition, thermal techniques only measure forward ejection fraction. However, placement of a second thermistor either in the atrium (for patients with mitral or tricuspid insufficiency) or in the right ventricle (for patients with a left to right shunt) would allow measurement of regurgitant or shunt fraction. We did not evaluate this potential in our study, but feel that this application warrants further work. In conclusion, thermal techniques can be used to measure ejection fraction, ventricular volumes, and cardiac output accurately and inexpensively. In these preliminary studies the technique has shown good results in a wide variety of applications. The complete potential and limitations of the technique have not been fully explored. APPENDIX: DILUTION
PRINCIPLES OF THERMAL VOLUME MEASUREMENT
Calculation of ejection fraction by radionuclear, angiographic, or echo techniques is basedupon measurement of the end diastolic (EDV) and end-systolic volumes (ESV). In contrast, calculation of EF by thermal techniques is based on conservation of energy. Ventricular volumes are then derived based upon a knowledge of cardiac output (CO) and heart rate (HR).
RAY
ET AL.: THERMAL
Conservation of energy requires
co =
T, (ESV)(C) + TB (EDV-ESV)(C) 69 (1) = Tz P;J)(C)
EJECTION
(1)
345
FRACTION
k area under the washout curve
where k = a constant related to injectate temperature and volume, stroke volume (SV) can be derived as
sv = co where T, = temperature of the blood in the ventricle during the first systole; TB = baseline blood temperature; T, = temperature of the blood in the ventricle during the second systole; and C = a constant related to the specific gravity and heat capacity of the blood. Term 1 is the heat energy of the blood in the ventricle at the end of the first systole. Term 2 is the heat energy of the blood that enters the ventricle during the following diastole. The sum of thesetwo energiesmust equal the energy in the ventricle when the two blood volumes are mixed and ejected during the second systole (Term 3). Ejection fraction (EF) is defined as the percent of the blood in the chamber at end diastole that is ejected at end systole or EDV-ESV cl-ESV EF = (2) EDV . EDV Rearranging Eq. (l), ESV T2 - TB =- TB - T2 -=(3) EDV T1 - TB TB - T, ’ Therefore ejection fraction can be calculated by measuring the incoming (baseline) blood temperature and two “ejected blood” temperatures. Substituting Eq. (3) into Eq. (2) EF=l-p
TB -
EF=l-
TB -
T2
TB - T, ’ To generalize this for any two systoles, the numbers 1 and 2 can be changed to i and i + 1: T+I
TB - Ti EF may be expressed as EF
= 1- 2
and
EF = 1 - %.
I Since CO can be calculated from the same thermal washout curve by the equation
HR’
Since EF = SV/EDV, EDV = $
and
ESV = EDV - SV.
Therefore, EF, CO, ESV, and EDV can be calculated after measuring the temperature of the ejected blood during consecutive systoles, the baseline blood temperature, the heart rate, and the area under the thermal washout curve. The only assumptions inherent in these equations are that (1) there is adequate mixing in the ventricle prior to ejection and (2) small fluctuations in ejected blood temperature can be measured accurately and rapidly. REFERENCES 1. American Edwards Laboratories, personal communication. 2. Berger, H. J., Matthay, R. A., Pyrlik, L. M., et al. First pass radionuclide assessment of right and left ventricular performance in patients with cardiac and pulmonary disease. Semin. Nucl. Med. 9: 275, 1979. 3. Bin& R. J., Heimbecker, R., and Falholt, W. An estimation of the residual volume of blood in the right ventricle of normal and diseased human hearts in vivo. Amer. Heart J. 42: 483, 1951. 4. Boak, J. G., Bove, A. A., and Krevlen, T. A geometric basis for calculation of right ventricular volume in man. Cathet. Cardiovasc. Diagn. 3: 217, 1977. 5. Calvin, J. E., Dredger, A. A., and Sibbald, W. J. Does the pulmonary capillary wedge pressure predict left ventricular preload in critically ill patients? Crit. Care Med. 9: 437, 1981. 6. Dehmer, G. J., Firth, B. G., Hills, L. D. et al. Nongeometric determination of right ventricular volumes from equilibrium blood pool scans. Amer. J. Cardiol. 49: 78, 1982. 7. Folse, R., and Braunwald, E. Determination of left ventricular volume ejected per beat and of ventricular end-diastolic and residual volumes. Circulation 25: 674, 1962. 8. Holt, J. P. Estimate of the residual volume of the
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ventricle of the dog’s heart by two indicator dilution techniques. Circ. Rex 4: 187, 1956. 9. Homer, L. D., and Krayenbuehl, H. P. A mathematical model for the estimation of heart volumes from indicator dilution curves. Circ. Res. 20: 299, 1967. 10. Iskandrian, A. S., Hakki, A. H., Kane, S. A., et al. Quantitative radionuclide angiography in assessment of hemodynamic changesduring upright exercise:observation in normal subjects, patients with coronary artery diseaseand patients with aortic regurgitation. Amer. J. Cardiol. 48: 239, 1981. 11. Latter, M. B., Strauss, H. W., and Pohost, G. M. Right and left ventricular geometry: Adjustments during acute respiratory failure. Crit. Care Med. 7: 509, 1979. 12. Mangano, D. T., VanDyke, D. C., and Ellis, R. J. The effect of increasing preload on ventricular output and ejection in man: Limitations of the Frank-Starling mechanism. Circulation 62: 535, 1980. 13. Martyn, J. A. J., Snyder, M. T., and Szyfelbein, S. K.: Right ventricular dysfunction in acute thermal injury. Ann. Surg. 191: 330, 1980. 14. Matthay, R. A., Berger, H. J., Loke, J., et al. Effects
of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: Non-invasive assessmentby radionuclide angiocardiography. Amer. J. Med. 65: 903, 1978. 15. Rigo, P., Alderson, P. O., Robertson, R. M., et al. Measurement of aortic and mitral regurgitation by gated cardiac blood pool scan. Circulation 60: 306, 1979. 16. Salgado,C. R., and Galletti, P. M. In vitro evaluation of thermodilution technique for measurement of ventricular stroke volume and end-diastolic volume. Cardiologica 49: 65, 1966. 17. Scholz, P. M., Rerych, S. K., Moran, J. F., et al. Quantitative radionuclide angiography. Cachet. Cardiovasc. Diagn. 6: 265, 1980. 18. Shah, P. K., Pichler, M., Berman, D., et al. Noninvasive identification of a high risk subsetof patients with acute inferior myocardial infarction. Amer. J. Cardiol. 46: 915, 1980. 19. Swan, H. J. C., and Beck, W. Ventricular non-mixing as a source of error in the estimation of ventricular volume by the indicatordilution technique. Circ. Rex 8: 989, 1969.
OF SURGICAL
Measurement
RESEARCH
34,
331-346 (1983)
of Ejection Fraction by Thermal Dilution Techniques’
HAROLD R. KAY, M.D., *** MANOUCHERAFSHARI, M.D.,* PAUL BARASH,M.D.,? WILLIAM WEBLER, B.S.M.E.,$ ABDULMASSIH ISRANDRIAN,
M.D.,5
CHARLESBEMIS, M.D.,5 A-HADI HAKKI, M.D.,* AND ELDREDD. MUNDTH, M.D.* *Department of Cardiothoracic Surgery and $Section of Cardiology, Hahnemann University, Philadelphia, Pennsylvania 19102, and the VDepartment of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut 06520, and *American Edwards Laboratories, Santa Ana, California 92711 Presented at the Annual Meeting of the Association for Academic Surgery, San Diego, California, November 7-10, 1982 The reproducibility, accuracy, and clinical applicability of ventricular ejection fraction derived by a thermal dilution technique were assessed in 22 dogs and 18 patients. Results obtained by the thermal technique were compared to simultaneous results obtained by radionuclide angiography. Right ventricular ejection fraction, measured in 9 dogs (1014 determinations) and 8 patients (744 determinations) was reproducible +5%. Left ventricular ejection fraction, measured in 10 patients, was reproducible f5W. Correlation between thermal and radionuclear measurements varied from 0.86 to 0.93 (all P < 0.02). We conclude that, because of its low cost, ease of use, and accuracy, thermally derived ejection fraction determinations can be helpful in hemodynamic monitoring of critically ill patients.
INTRODUCTION
Precise measurement of ejection fraction has potential prognostic [ 181,diagnostic, and therapeutic [ 12, 131advantages. However, logistic constraints imposed by existing techniques preclude routine measurement of these indices in critically ill patients. The three currently available methods (radionuclear angiography, contrast angiography, and echocardiography) all require large, expensive imaging systems and special personnel which make it difficult to accurately monitor ejection fraction at the bedside. In addition, the risk to the patient from accumulated radiation or from repetitive angiographic dye injections make it difficult to perform serial measurements. Knowledge of ejection fraction may be critical in pre- and postoperative care of patients with poor ventricular function in whom early recognition of impending ventricular dysfunction might allow earlier, more effective ’ Supported in part by a grant from American Edwards laboratories, Santa Ana, California. * To whom requests for reprints should be sent at Department of Cardiothoracic Surgery, Hahnemann University, 230 North Broad St., Philadelphia, Penn. 19102. 337
intervention. In addition, becauseventricular compliance can change rapidly in the compromised ventricle [ 121, therapy directed at “optimization” of filling pressures may not improve ventricular performance [5]. The principle of using indicator solutions to measure residual volume (the volume of blood remaining in the ventricle during isometric relaxation) was described by Holt [8] and confirmed by Salgado [ 161.Bing [3] has discussed the principles of right ventricular residual volume measurement. Unfortunately, early investigations with the use of an iced saline bolus as an indicator solution were frustrated by inadequate technology; the response time of the thermistor was only 300 msec. Although this response time is adequate for calculation of cardiac output, it is too slow for calculation of ventricular volumes. Currently available mounted thermistors have an average response time of only 1000 msec [l]. A recent technological advance has allowed manufacture of mounted thermistors with a responsetime of 50 msec. This rapid response thermistor is fast enough to measure beatto-beat temperature variations and allows 0022-4804/83 $1 SO Copyright 0 1983 by Academic Press. Inc. All rights of reproduction in any form reserved.
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JOURNAL OF SURGICAL RESEARCH: VOL. 34, NO. 4, APRIL 1983
FIG. 1. Position and configuration of the modified Swan-Ganz catheter in either the canine or human
calculation of ventricular volumes (see Appendix). This study was designed to evaluate the reproducibility, accuracy, and clinical applicability of the thermal technique to calculate ejection fraction in both the right and left ventricles. MATERIALS
AND
METHODS
The study was conducted using both animal and human subjects. Preliminary investigations regarding modeling technique, computer algorithms, and optimum injectate temperature and volume were assessedin a canine right ventricle model (CANINE RIGHT VENTRICLE). Subsequent human investigations were conducted either in patients undergoing cardiac operations (HUMAN RIGHT VENTRICLE) or cardiac catheterization (HUMAN LEFT VENTRICLE). Informed consent was obtained for all human
studies under a protocol approved by the Human Studies Committee. Canine Right Ventricle Twenty-two mongrel dogs were anesthetized using pentobarbitol, intubated and ventilated with a volume-limited respirator. A 7F Swan-GanzB3catheter, modified with a rapid response thermistor, and manufactured with dimensions appropriate for a dog, was positioned into the pulmonary artery via a percutaneous jugular venous cutdown (Fig. 1). In addition to the right ventricular and pulmonary artery pressures(recorded through the various ports of the Swan-Ganz@ catheter), femoral artery pressureand pulmonary artery temperature were continuously monitored and stored on a physiologic tape recorder. An American Edwards Model 9310 Lung 3 %wan-Ganz is a registered trademark of American Edwards Laboratories.
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Water Computer was modified using a preprogrammed computer microchip to allow amplification of the thermistor output signal (pulmonary artery temperature) and calculation of cardiac output. Ejection fraction was calculated using the formulas in Figs. 2 and 3 (see Appendix), Continuous intravenous isoproterenol and volume loading were used to increase right ventricular ejection fraction (RVEF) from 3540% (normal RVEF) to 55-70% (high RVEF). These agents also increased heart rate and cardiac output. Ejection fraction was decreased to 17-30% (low RVEF) by increasing right ventricular afterload (intravenous neosynephrine or respiratory acidosis). At all three levels of ejection fraction (normal, high, and low) injectate site (right atrium or right ventricle), volume (3, 5, or 10 ml), and temperature (4 or 24°C) were randomly varied. Multigated equilibrium blood pool imaging was performed using in vivo labeling of red blood cells with unlabeled stannous pyrophosphate before injecting 12-l 5 mc of technetium-99m or sodium pertechnetate. The dogs were positioned in the lateral projection, and the camera in 30” LAO projection with lo- 15’ caudal angulation. This was the best projection to separate the right ventricle and the left ventricle. Collection of data was performed with a standard gamma scintillation camera (series 420 Mobile Gamma
RF = Mean
Residual
Fraction
0.5oc I
FIG. 2. A typical thermal washout curve. The thermal bolus is injected immediately after the 0S”C standard. The plateaus on the downslope portion of the curve rep resent diastole when there is little flow and therefore little change in temperature. C, , C,, and C, represent the differencesin temperature between baseline and the respective diastoles. Note a decreasein temperatures is an upward deflection of the curve.
339
EJECTION FRACTION sv = COIHR CO = k,SrSS under the thermal EDV = SVlEF ESV = EDV _ ESV Where Sv = Stroke Volume co = csrdisc output k = A Constant EDV = End Diastolic Volu”%* EF = Ejection Friction ESV = End Systolic Volume
washout
Curve
FIG. 3. Formulas to obtain stroke volume, cardiac output, end-diastolic volume, and end-systolic volume from the thermal washout curve.
Camera, Technicare) equipped with a low energy all-purpose collimater. The image data were acquired with a dedicated nuclear medicine minicomputer (VIP 550, Technicare) and formatted into a 64 X 65 matrix. A mean R-R interval was determined by averaging five beats immediately prior to data acquisition and data were divided into 16 equal frames. Cardiac cycles with R-R intervals greater than 20% of the mean R-R interval were rejected. A total of 250,000 counts/frame were accumulated in the whole field of view. The energy window (20%) of the gamma camera was set symmetrically around the 140 keV photo peak. Regions of interest were drawn over the right ventricle by visual inspection taking care to include the entire right ventricle while excluding as much of the right atrium and pulmonary artery as possible. The end-diastolic and end-systolic frames were identified and smoothed with a nine point centerweighted filter. Background correction was performed by a linear interpolated subtraction technique. Separate right ventricular regions of interest were constructed for the end-diastolic and end-systolic frames. The frames were displayed in endless loop movie format to assist in identification of ventricular borders. The right ventricular ejection fraction was calculated r+ end-diastolic counts - end-systolic counts end-diastolic counts x 100. Human Right Ventricular Studies
Eight patients scheduled to undergo elective cardiac operations were used to evaluate
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the reproducibility and accuracy of serial determinations of ejection fraction during the perioperative period. Prior to induction of anesthesia a SwanGanz@ catheter, modified with a rapid response thermistor, was positioned into the pulmonary artery (Fig. 1). The operation then proceeded in the routine fashion, At various times during the operation right ventricular ejection fraction was determined. At the conclusion of the operation patients were transferred to the intensive care unit and ejection fraction was calculated whenever a determination of cardiac output was clinically indicated. No pharmacologic manipulations were carried out except as clinically indicated. On the third postoperative day a first-pass radionuclide angiogram was done and left and right ventricular ejection fraction and cardiac output were calculated. Thermal ejection fraction, cardiac output, and ventricular volumes were measured simultaneously. lnjectate volume (5 or 10 ml), site (right atrium or right ventricle) and temperature (4 or 24°C) were varied to assessthe accuracy of ejection fraction as a function of differing injectate parameters. All thermal measurements were done in duplicate or triplicate and the results averaged. Human Left Ventricular Studies Ten patients undergoing elective cardiac catheterization for a variety of indications participated in the study. A 3F probe with a rapid response thermistor was inserted percutaneously into the femoral artery and positioned in the ascending aorta. A separate catheter was positioned into the left atrium (via a patent foramen ovale or retrograde across the mitral valve) or retrograde across the aortic valve into the left ventricle. Left ventricular ejection fraction and volumes were calculated following either ( 1) a 10 ml saline bolus into either the left atrium or left ventricle, or (2) injection of angiographic dye into the left ventricle (routine ventriculogram). A first-pass radionuclide angiogram was
performed in all patients at the conclusion of the cardiac catheterization. Left ventricular volumes were calculated by radionuclide, thermal, and contrast angiographic techniques. The results of these three techniques were compared. In human subjects the right and left ventricular ejection fractions were determined in the anterior projection by the first-passmethod using a computerized multicrystal camera (Baird-Atomic Systems-77, Bedford, Mass.). The ejection fraction was determined from the background corrected cardiac cycle as end-diastolic counts - end-systolic counts end-diastolic counts x 100. The method has previously been described by this and other laboratories [2, 10, 171. Data Analysis Reproducibility of calculations was determined by comparing consecutive determinations under steady state conditions. Accuracy of thermal-derived values was assessed by comparison to simultaneously derived radionuclide or angiographic values. Comparison between consecutive measurements (reproducibility) or between different thermal and nuclear measurements (accuracy) was determined using analysis of variance, paired t test, correlation coefficient analysis, and linear regressiontechniques. All data is expressedas mean f standard error and a P value of co.05 was considered significant. RESULTS
Canine Right Ventricle Figure 4 graphs the results of 329 pairs of consecutive ejection fraction determinations following a saline bolus into the right atrium. The determinations were done under steady stateconditions (normal, high, or low ejection fraction) using different injectate temperatures (4 or 24°C) and volumes (3, 5, or 10 ml). Figure 5 graphs the results following saline injections into the right ventricle.
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The results after right ventricular injections are less reproducible than the results after right atria1 injections which is probably a function of inadequate mixing during right ventricular injections [ 191. When the RA and RV injection data are pooled, the 70% confidence limit is 6%, implying that consecutive determinations are reproducible f6%. Injectate volume and temperature had no significant effect on measured ejection fraction. Figure 6 shows the comparison between ejection fraction simultaneously measured by thermal and multigated blood pool imaging techniques. Although the correlation is reasonable, (I = 0.9) and significant (P < 0.01) the regression equation is
Y = 0.92(X) + 18. The high intercept value of 18 suggests that either the gated technique consistently underestimates ejection fraction or the thermal technique consistently overestimates ejection fraction. However, the slope of the equation (0.92) implies that, once the 18% effect is taken into consideration, increases or decreases in ejection fraction are accurately reflected by either technique.
Human Right Ventricle
EJECTION
FRACTION
RVEFSECOND INJECTION
341
40.
FIG. 5. Comparison between consecutive thermal ejection fractions in the canine right ventricle following a thermal bolus into the right ventricle.
crepancy is accentuated in patients with low ejection fractions (~25%). When ejection fraction is >30% the data points are in closer alignment. When consecutive thermal determinations (372 pairs) of ejection fraction are compared under steady state conditions, the reproducibility of the determination (70% confidence limit) is +-5%. As in the dog model, right atria1 injections are more reproducible than right ventricular injections and injectate volume (5 or 10 ml) and temperature (4 or 24°C) have no significant effect on the measurement.
Human Left Ventricle
Figure 7 graphs the results of a comparison of simultaneously measured thermal and firstpass studies in 10 patients. Examination of individual data points shows again that the nuclear determination is lower than the thermal values and the dis-
RVEF40. SECOND INJECTIONM. w x). r = 0.80 P
FIG. 4. Comparison between consecutive ejection fractions in the canine right ventricle following a thermal bolus into the right atrium.
Figure 8 shows the comparison between first-pass and thermal measurements in the human left ventricle. The data compares 19 thermal determinations in 10 patients. Nuclear ejection fraction was measured only once in each patient. Ten thermal data points represent the results following a saline injection into the left atrium. The additional 9 thermal data points represent the measured ejection fraction following a 30-40 ml room temperature injection of angiographic dye into the left ventricle. The highly significant correlation coefficient (r = 0.93, P < 0.00 1) and virtual identity of the linear regression line substantiate the accuracy of thermally derived left ventricular ejection fraction. Injectate site (left atrium or ventricle), tem-
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60 ‘. 50 THERMAL RVEF (%I
40
I::
40
10
GATED%“CLEAYi)R (%I
RVEF
FIG. 6. Comparison between thermal and gated nuclear determinations of ejection fraction in the canine right ventricle.
perature (4 or 24”C), and composition (saline or angiographic dye) had no significant effect on calculation of ejection fraction. A total of 342 determinations of ejection fraction were calculated in the 10 patients. The calculated ejection fraction was reproducible +5% (70% confidence limit). DISCUSSION
Thermal techniques provide a convenient, inexpensive, safe, and accurate method of measuring cardiac output, ejection fraction, and ventricular volumes. The technique is particularly appealing for serial monitoring of right ventricular function for it is no more invasive than the insertion of a Swan-Ganz@ catheter. Our studies show that repetitive measurements of ejection fraction are reproducible t5% even at extreme ranges of ejection fraction. This reproducibility compares favorably with other techniques. Unfortunately there is no “gold standard” against which to compare thermally derived right ventricular ejection fraction. In our dog studies we compared thermally derived ejection fraction to results obtained from a multigated blood pool imaging technique. However, adequate separation of the right ventricle from left ventricle and adequate definition of right ventricular borders are difficult in the animal model, resulting in contamination with data derived from the right atrium and possibly also cutting off some counts from the region of the outflow tract. We suspect that
this accounts for the discrepancy between the nuclear and thermal values in the animal study. This problem with right ventricle gated images has been described in man [ 15, 171 and may be more pronounced in the dog [6]. Despite the problems inherent in the gated technique, it is encouraging that the correlation coefficient between the two techniques is still good (r = 0.86, P < 0.01) implying that changes in right ventricular ejection fraction are accurate, although the nuclear values are consistently lower. The first-pass technique is less subject to errors in measurement because it is a timephase study in which the isotopic tracer is followed from the great veins through the right atrium, right ventricle, and out into the pulmonary artery. Therefore, by selecting appropriately timed frames, radioactivity can be counted at the precise time that the isotope bolus is in the appropriate (RA, RV, or PA) location. When the thermal and first-pass techniques are compared in the human right ventricle, not only is the correlation good (r = 0.90, P < 0.01) but the slope of the regression line approaches 1 and the offset (Y intercept) of the regression line is virtually zero. We are therefore confident that the thermally derived right ventricular ejection fraction is an accurate measurement. Studies on the left ventricle increase confidence in the thermal technique because the
THERMAL RVEF (W 25. Iy=10 r=o.w p
PASS
d:LEAR w
RVEF
FIG. 7. Comparison between thermal and first-passradionuclear determination of ejection fraction in the human right ventricle.
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accuracy of the first-pass technique in the left ventricle is well established. There is good correlation (r = 0.93, P < 0.001) between thermal and nuclear techniques in the human left ventricle. The accuracy of the thermal determination is supported by the slope (virtually 1) and the offset (virtually 0) of the regression line. The first-pass technique to assessventricular volumes is subject to measurement errors (defining the precise borders of the left ventricle), geometric assumptions, attenuation, or overlap of counts. Both angiographic and echocardiographic techniques are subject also to even greater assumptions about ventricular geometry [4, 7, 93. Since the thermal technique is not encumbered by these constraints, we suspectthat, at least theoretically, the thermal technique is potentially more accurate than the other techniques. Assuming that the thermal technique is both accurate and reproducible, the final consideration is its applicability to patient care. The use of serial right ventricular function monitoring is intrinsically less appealing than is monitoring of left ventricular function because clinicians have always had the concept that the left ventricle is more important. While the left ventricle usually is, there are numerous situations when decreased right ventricular function (secondary to ischemia or pulmonary hypertension) precludes adequate right heart output to a normal left ventricle [ 11, 141.In these situations right ventricular function must be optimized before systemic perfusion improves. In other circumstances monitoring right ventricular performance may be extremely important (such as in patients after mitral valve replacement, especially those with pulmonary hypertension, and in patients with chronic obstructive pulmonary disease, pulmonary embolus, adult respiratory distress syndrome, etc.). If serial monitoring of right ventricular performance were readily available, therapeutic regimens could be titrated against objective measurements of right ventricular parameters. Despite the absence of intrinsic appeal of
EJECTION
FRACTION
343
FIG. 8. Comparison between thermal and first-pass radionuclear determination of ejection fraction in the human leti ventricle.
right ventricular ejection fraction as contrasted with the left ventricle, right ventricular volume determinations are easily performed and require no more invasive technology or risk than the risk to which the patient has already been subjected, namely the risk inherent in the insertion of a Swan-Ganz@catheter and determination of cardiac output. The same saline injection that is routinely used for cardiac output determination could be used to calculate ejection fraction, end-diastolic volume, and end-systolic volume. If right atrial and right ventricular pressures are recorded from the Swan-Ganz@catheter, right ventricular pressure-volume relations can be studied. While this may be hemodynamic overkill, the patient risk factor is not increased and the critically ill patient may potentially benefit by an increased physician awareness of the hemodynamic status. In contrast to right ventricular volume determinations, measurement of left ventricular ejection fraction is intrinsically more appealing and its potential application is more widespread. However, left ventricular ejection fraction monitoring entails a significant risk for the patient. There are two areas in which the thermal left heart ejection fraction technique might find clinical application: the cardiac catheterization laboratory and the monitoring of critically ill patients either after cardiac operation or in the intensive care unit. In the catheterization laboratory, serial or sequential measurements of ejection fraction
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with various interventions could be performed by multiple saline injections, without the risk and inconvenience of multiple contrast angiograms. Our data indicate that LVEF and volumes can be reliably measured. Left ventricular ejection fraction and volumes can also be accurately measured using the renographin-76 as a thermal bolus and thus obviating the need for geometric assumptions in the calculations. The risks of serial measurement of left-sided ventricular volumes are twofold: (1) the risk of left-sided thrombus on the catheter with arterial embolism and (2) the risk of arterial air embolism at the time of the bolus injection. The first risk is minimal in the catheterization laboratory as most patients are anticoagulated during the procedure. The second problem, air embolism, is of greater concern, but is something that is routinely done during coronary arteriography. The problems with clot or air embolus are of greater concern if the technique is used in patients outside the catheterization laboratory. Recently, work has shown that heparincoated catheters may reduce the amount of thrombosis. Although the risk of air embolus has to be considered, many postoperative cardiac surgery units already monitor left atria1 pressure. With extreme caution this left atria1 line could be used for introduction of the saline bolus. The potential benefit of measurement of left ventricular ejection fraction must be weighed against the potential risk. We suspect that the knowledge of ejection fraction and left ventricular distention (increased end-diastolic volume) that could be gained from this technique in patients with borderline left ventricular function may outweigh the risk factor. Two other potential problems exist in any determination of ventricular volumes. The first regards measurement of ejection fraction in patients with an irregular heart rate. All techniques to measure ejection fraction will show beat-to-beat variation as a function of diastolic filling time. We have not studied the
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effect of varying diastolic filling time on calculated ejection fraction. However, one patient in our serieswas in atrial fibrillation during part of the study. An analysis of his thermal curves showed a good beat-to-beat correlation between a prolonged diastolic filling time and an increased ejection fraction. Becausethe thermal technique has the potential to measure ejection fraction for 4 or 5 consecutive beats, the average ejection fraction during these 4 or 5 beats could be calculated. Alternatively, the ejection fraction could be calculated for each individual beat, thus deriving a maximum and a minimum ejection fraction. A second problem (or advantage) of the thermal technique regards its applicability in patients with A-V valve regurgitant lesions or intracardiac shunts. By definition, thermal techniques only measure forward ejection fraction. However, placement of a second thermistor either in the atrium (for patients with mitral or tricuspid insufficiency) or in the right ventricle (for patients with a left to right shunt) would allow measurement of regurgitant or shunt fraction. We did not evaluate this potential in our study, but feel that this application warrants further work. In conclusion, thermal techniques can be used to measure ejection fraction, ventricular volumes, and cardiac output accurately and inexpensively. In these preliminary studies the technique has shown good results in a wide variety of applications. The complete potential and limitations of the technique have not been fully explored. APPENDIX: DILUTION
PRINCIPLES OF THERMAL VOLUME MEASUREMENT
Calculation of ejection fraction by radionuclear, angiographic, or echo techniques is basedupon measurement of the end diastolic (EDV) and end-systolic volumes (ESV). In contrast, calculation of EF by thermal techniques is based on conservation of energy. Ventricular volumes are then derived based upon a knowledge of cardiac output (CO) and heart rate (HR).
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Conservation of energy requires
co =
T, (ESV)(C) + TB (EDV-ESV)(C) 69 (1) = Tz P;J)(C)
EJECTION
(1)
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FRACTION
k area under the washout curve
where k = a constant related to injectate temperature and volume, stroke volume (SV) can be derived as
sv = co where T, = temperature of the blood in the ventricle during the first systole; TB = baseline blood temperature; T, = temperature of the blood in the ventricle during the second systole; and C = a constant related to the specific gravity and heat capacity of the blood. Term 1 is the heat energy of the blood in the ventricle at the end of the first systole. Term 2 is the heat energy of the blood that enters the ventricle during the following diastole. The sum of thesetwo energiesmust equal the energy in the ventricle when the two blood volumes are mixed and ejected during the second systole (Term 3). Ejection fraction (EF) is defined as the percent of the blood in the chamber at end diastole that is ejected at end systole or EDV-ESV cl-ESV EF = (2) EDV . EDV Rearranging Eq. (l), ESV T2 - TB =- TB - T2 -=(3) EDV T1 - TB TB - T, ’ Therefore ejection fraction can be calculated by measuring the incoming (baseline) blood temperature and two “ejected blood” temperatures. Substituting Eq. (3) into Eq. (2) EF=l-p
TB -
EF=l-
TB -
T2
TB - T, ’ To generalize this for any two systoles, the numbers 1 and 2 can be changed to i and i + 1: T+I
TB - Ti EF may be expressed as EF
= 1- 2
and
EF = 1 - %.
I Since CO can be calculated from the same thermal washout curve by the equation
HR’
Since EF = SV/EDV, EDV = $
and
ESV = EDV - SV.
Therefore, EF, CO, ESV, and EDV can be calculated after measuring the temperature of the ejected blood during consecutive systoles, the baseline blood temperature, the heart rate, and the area under the thermal washout curve. The only assumptions inherent in these equations are that (1) there is adequate mixing in the ventricle prior to ejection and (2) small fluctuations in ejected blood temperature can be measured accurately and rapidly. REFERENCES 1. American Edwards Laboratories, personal communication. 2. Berger, H. J., Matthay, R. A., Pyrlik, L. M., et al. First pass radionuclide assessment of right and left ventricular performance in patients with cardiac and pulmonary disease. Semin. Nucl. Med. 9: 275, 1979. 3. Bin& R. J., Heimbecker, R., and Falholt, W. An estimation of the residual volume of blood in the right ventricle of normal and diseased human hearts in vivo. Amer. Heart J. 42: 483, 1951. 4. Boak, J. G., Bove, A. A., and Krevlen, T. A geometric basis for calculation of right ventricular volume in man. Cathet. Cardiovasc. Diagn. 3: 217, 1977. 5. Calvin, J. E., Dredger, A. A., and Sibbald, W. J. Does the pulmonary capillary wedge pressure predict left ventricular preload in critically ill patients? Crit. Care Med. 9: 437, 1981. 6. Dehmer, G. J., Firth, B. G., Hills, L. D. et al. Nongeometric determination of right ventricular volumes from equilibrium blood pool scans. Amer. J. Cardiol. 49: 78, 1982. 7. Folse, R., and Braunwald, E. Determination of left ventricular volume ejected per beat and of ventricular end-diastolic and residual volumes. Circulation 25: 674, 1962. 8. Holt, J. P. Estimate of the residual volume of the
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ventricle of the dog’s heart by two indicator dilution techniques. Circ. Rex 4: 187, 1956. 9. Homer, L. D., and Krayenbuehl, H. P. A mathematical model for the estimation of heart volumes from indicator dilution curves. Circ. Res. 20: 299, 1967. 10. Iskandrian, A. S., Hakki, A. H., Kane, S. A., et al. Quantitative radionuclide angiography in assessment of hemodynamic changesduring upright exercise:observation in normal subjects, patients with coronary artery diseaseand patients with aortic regurgitation. Amer. J. Cardiol. 48: 239, 1981. 11. Latter, M. B., Strauss, H. W., and Pohost, G. M. Right and left ventricular geometry: Adjustments during acute respiratory failure. Crit. Care Med. 7: 509, 1979. 12. Mangano, D. T., VanDyke, D. C., and Ellis, R. J. The effect of increasing preload on ventricular output and ejection in man: Limitations of the Frank-Starling mechanism. Circulation 62: 535, 1980. 13. Martyn, J. A. J., Snyder, M. T., and Szyfelbein, S. K.: Right ventricular dysfunction in acute thermal injury. Ann. Surg. 191: 330, 1980. 14. Matthay, R. A., Berger, H. J., Loke, J., et al. Effects
of aminophylline upon right and left ventricular performance in chronic obstructive pulmonary disease: Non-invasive assessmentby radionuclide angiocardiography. Amer. J. Med. 65: 903, 1978. 15. Rigo, P., Alderson, P. O., Robertson, R. M., et al. Measurement of aortic and mitral regurgitation by gated cardiac blood pool scan. Circulation 60: 306, 1979. 16. Salgado,C. R., and Galletti, P. M. In vitro evaluation of thermodilution technique for measurement of ventricular stroke volume and end-diastolic volume. Cardiologica 49: 65, 1966. 17. Scholz, P. M., Rerych, S. K., Moran, J. F., et al. Quantitative radionuclide angiography. Cachet. Cardiovasc. Diagn. 6: 265, 1980. 18. Shah, P. K., Pichler, M., Berman, D., et al. Noninvasive identification of a high risk subsetof patients with acute inferior myocardial infarction. Amer. J. Cardiol. 46: 915, 1980. 19. Swan, H. J. C., and Beck, W. Ventricular non-mixing as a source of error in the estimation of ventricular volume by the indicatordilution technique. Circ. Rex 8: 989, 1969.