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Evaluation of left ventricular function by impedance cardiography: A review
Progress in
Cardiovascular Diseases VOL XXXVI, NO 4
JANUARY/FEBRUARY 1994
Evaluation of Left Ventricular Function by Impedance Cardiography: A Review Hugh D. Fuller
VER THE PAST 20 years the bedside measurement of ventricular function has become a standard in the critically ill because of the development of the pulmonary artery (PA) catheter. 1 Despite this development, there is, to date, conflicting evidence and opinion as to the benefit to patients of this maneuver, 2-6and it has a low but important risk of major morbidity and mortality.7-n Although it may not be possible to reach a solid conclusion as to the overall benefit of the PA catheter, the same information accurately and reliably collected by a noninvasive technique (without risk from adverse side effects) would be more acceptable because of its more favorable risk-benefit ratio. Impedance cardiography~2 is a noninvasive technique that measures the impedance of a low-current, high-frequency alternating current across the thorax. From measured changes in thoracic impedance associated with the cardiac cycle, calculation of stroke volume (SV) and cardiac output can been made and has been shown to correlate moderately well with concurrently measured thermodilution cardiac output. 13-27It has also been suggested that measurements from thoracic impedance tracings may predict various markers of ventricular function. If this is true, then impedance cardiography may be able to provide as much hemodynamic information as the PA catheter and may make use of the PA catheter unnecessary in many cases. The remainder of this review will discuss the data relating to impedance prediction of ventricular function. Studies reviewed here were sought by an extensive MEDLINE search (from 1966 to present) of articles relating to impedance cardiography and ventricular function, ejection fraction
O
(EF), end-distolic volume (EDV), and systolic time intervals. In addition, studies cited by other articles were sought, and reports in the advertising literature distributed by impedance cardiograph manufacturers were also reviewed. Finally, reports from contracts sponsored by the National Aeronautics and Space Administration (Houston, TX) were obtained and reviewed. In this way, a complete review of the existing literature was obtained. SYSTOLIC TIME INTERVALS
It has been established that in hearts with reduced ventricular function the ratio of the preejection period to ventricular ejection time (PEP/VET) is increased. Garrard et aF s confirmed this, finding a good negative correlation between PEP/VET, calculated from electrocardiogram (ECG) and aortic pressure tracings, and radionuclear EF measurements (r = -.90). Using a combination of ECG and impedance tracings (see Fig 1), both PEP and VET can be calculated, allowing prediction of ventricular function by impedance. A number of studies have examined the relationship between impedance-calculated PEP/VET and radionuclear measurements of EF. Capan et a129 reported results from 26 patients with ischemic or myopathic heart disease who underwent simultaneous impedance From the Department of Medicine and the Regional Critical Care Program, McMaster University, Hamilton, Ontario, Canada. Address reprint requests to Hugh D. Fuller, MB, MSc, FRCPC, Department of Medicine, St Joseph's Hospital, 50 Charhon Ave E, Hamilton, Ontario, Canada, L8N 4A6. Copyright 9 1994 by W.B. Saunders Company 0033-0620/94/3604-000155.00/0
Progress in Cardiovascular Diseases, Vol XXXVI, No 4 (January/February), 1994: pp 267-273
267
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HUGH D. FULLER
dZ/dt
/ A wave q-Z
PEP
ECG
and gated-pooled scans. A linear relationship between the two techniques was established, and a moderately good negative correlation (r = - . 8 5 ) was found. The equation derived from this relationship was then used to predict EF by impedance. Using Capan's equation for calculation of impedance EF, Appel et aP ~ reported on 32 intensive care unit (ICU) patients, who underwent simultaneous impedance and gated-pooled scans. The results show correlation to be only fair when EF was greater than 40% (r = .7) and to be very poor when EF was lower. Hanna et aP 1 studied 17 volunteers who did not have heart disease before undergoing minor surgical procedures. Two were excluded because of ventricular ectopy, and single paired readings of impedance and radionuclear EF were performed on remaining volunteers. There was good correlation between impedance and gated-pooled EF (r -- .90), but poorer correlation between impedance and first-pass radionuclear EF (r = .77). However, the impedance EF for the first-pass studies was calculated from 16 consecutive heart beats, whereas the firstpass radionuclear EF involves only 4 or 5 beats per ventricle. Therefore, this discrepancy may account for the poorer correlation with first pass. From these studies, there appears to be moderately good validity of impedance PEP/ VET for prediction of left ventricular EF (LVEF) although it may be less accurate in critically ill patients. 3~ Studies examining the response of PEP/VET to various maneuvers were also reviewed. Hill et
Fig 1. First time derivative of impedance waveform (dZ/dt) and ECG are shown to demonstrate the following features: systolic time intervals (PEP and VET), C wave (maximum acceleration of blood during ventricular systole), A wave (caused by atrial systole), Tz (the sum of C wave height and A wave height), and q-Z (the interval from the start of electrical ventricular systole to the point of maximum acceleration of blood during systole).
aP 2 performed head-up and head-down tilts in a well-constructed study. The investigators used five normal volunteers, who maintained each position for 5 minutes before measurement and returned to supine baseline between postural changes. Impedance PEP/VET decreased by 12.1% in the head-down position, because of increased cardiac filling and output, and increased by 61.5% in the head-up position, because of reduced cardiac filling and output. Linde et a133,34performed a double-blind crossover study of the calcium blocker Nisoldipine in patients with congestive heart failure (CHF). A reduction in impedance PEP/VET was observed as a result of an increase in ventricular function while taking Nisoldipine. Smith et a135 measured impedance PEP/VET in six volunteers at rest and at two levels of exercise. The PEP/VET was reduced on exercise (P < .05) because of the increase of cardiac output and EF. Therefore, there is good evidence that impedance PEP/VET responds appropriately to maneuvers that produce clinically significant change. THE HEATHER INDEX
In 1969, Heather suggested a new index of cardiac function based on the impedance tracing. 36 He made impedance recordings on 14 patients undergoing cardiac catheterization, 7 of whom had valvular problems. He calculated the ratio of C wave height to the time to peak of C wave, C/(q - Z), (see Fig 1) and found that
IMPEDENCE CARDIOGRAPHY FOR LV FUNCTION
in a group of 4 patients with New York Heart Association (NYHA) grade III-IV functional capacity, this index was markedly lower than in those with N Y H A grade I or II (P = .001). A number of sources support the accuracy of this index. Hubbard et aP 7 performed impedance recordings on 37 patients with a clinical diagnosis of CHF. The Heather index was low in all of these patients, but this was a descriptive study and did not mention absolute levels nor did it compare readings with those in patients without heart failure. Richards et a138 made impedance recordings on 74 patients with a variety of heart diseases (but no functional capacity was recorded) and on 22 normal volunteers. Recordings were made in the supine position followed by sitting and then standing, but without return to the supine baseline. The Heather index in the normal volunteers decreased from supine to sitting position, presumably because of reduction in cardiac output, but this decrease was not significant. In the supine position, the patients had Heather indexes significantly lower than those for the normal volunteers (P < .05); however, the values increased significantly for patients but not for volunteers (P < .05) on transferring from the supine to sitting position. A semiquantitative subgroup analysis of the patient group showed that those patients taking vasodilators (presumably those with more severe disease) had the greatest reduction when in the supine position and had the greatest response to postural change. Therefore, this study shows an expected reduction in the Heather index in patients with heart disease that is likely to be greatest in those with more severe disease, presumably because of reduced cardiac function. The response to change from the supine to sitting position is to be expected on the basis of off-loading an overloaded left ventricle through this postural maneuver. The degree of benefit from this maneuver is likely to be greatest in those with the worst heart function. Better quantification of cardiac function in the patient group would have allowed more confidence in this interpretation. Two other studies also showed response of the Heather index to change. Linde et a133,34 showed an increase in the Heather index after Nisoldipine administration to subjects with heart disease, presumably caused by off-loading of
269
overloaded ventricles. Smith et a135 also showed an increase of 26% (not statistically significant) after steady-state exercise. Correlation of the Heather index with impedance P E P / V E T was performed by Hill et a132in five healthy subjects. Impedance recordings were made repeatedly after 5 minutes in each of the following positions: supine, head-down 30 ~, supine, head-up 40 ~ and supine. A total of 100 paired measurements were made, and a correlation coefficient of 0.79 was found between P E P / V E T and the Heather index. A study by Celsi et a139measured reliability by calculating the Heather index from impedance recordings taken twice in the same day on 10 normal subjects. The coefficient of variation for this value was acceptable at 14.5%. Therefore, these studies show that the Heather index has moderate validity as a measure of ventricular function and shows moderate reliability and good responsiveness to clinically significant change. CONTRIBUTION OF A WAVE HEIGHT
Judy et al 4~ have suggested that C/Tz from the first time derivative of the impedance tracing (see Fig 1) predicts EF and have published two abstracts in support of this claim. In the first abstract, 4~ impedance EF was calculated in 15 hypovolemic ICU patients subjected to a fluid challenge of 1,200 mL. EF decreased by 2.4% +_ 0.5% (SEM) as the wedge pressure increased 9 -+ 0.8 mm Hg. No further details are given, and the only conclusion that can be made is that this measurement responds to fluid challenge similar to EF, in a situation that produced an expected increase in wedge pressure. The second abstract 41 compared impedance and firstpass radionuclear EF in 493 patients in sinus rhythm with normal valve function. He divided the subjects into three groups, those with normal function, those with ischemia, and those with heart failure, but did not further define these groups. The mean and standard deviation of impedance EF was very close to that of radionuclear EF (formal statistical analysis was not applied), but there was very little difference between the mean EF in the three groups (64.8%, 49.7%, and 58.7%, respectively); therefore, little can be inferred from such a narrow range of values.
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HUGH D. FULLER
Although these two abstracts suggest that C/Tz may at least in part reflect EF, there are two theoretical concerns regarding its validity. First, its calculation requires the presence of an A wave (associated with atrial contraction) in the impedance tracing. Many critically ill patients are in atrial fibrillation; therefore, accurate calculation using this method will not be possible in these patients. Second, EF represents the ratio of ejected volume to total diastolic volume of blood, but the impedance calculation represents a ratio of accelerations rather than volumes. Therefore, intuitively it would appear not to have a solid theoretical base, thus making it less likely to be a valid calculation. Miles et aP e more recently compared impedance EF (calculated as C/Tz) with radionuclear EF in 95 patients with a variety of cardiovascular and other diseases, 7 of whom had unspecified arrhythmias. However, the techniques were not measured simultaneously, and the correlation between the two techniques was poor (r = - . 0 4 ) . Somewhat better correlation was observed by Fuller et al, 43 however, using single measurements in 15 patients with suspected or proven heart disease, 12 in sinus rhythm, and 3 in atrial fibrillation. Concurrent measurement of impedance tracing and radionuclear EF gave a correlation between C/Tz and EF of r = .51, still not adequate for clinical prediction of EF. Therefore, it would appear that on both theoretical and experimental grounds, C/Tz is unlikely to be a valid indicator of true EF.
HEIGHT OF THE O WAVE
The O wave (see Fig 2) is a small upward deflection in the first time derivative of the impedance waveform, occurring in midcardiac cycle. Lababidi et a144 found in 10 patients with mitral stenosis that the O wave peak occurred coincident with or within 0.01 second of the opening snap. Therefore, it is reasonable to assume that the O wave represents passive blood flow from atrium to ventricle during diastole. The presence of an enlarged O wave has been noted by several investigators 37,45 in patients with evidence of CHF. In some of these patients, particularly those with more severe disease, the enlarged O wave is present at all times. In others it is normal when supine but becomes enlarged in the head-down and legselevated positions, which is presumably caused by increased cardiac filling that worsens the degree of ventricular dysfunction. Calculation of the ratio of O wave height to C wave height (O/C; see Fig 2) was said by Donovan et a115 to be abnormal if it exceeded 0.3. He found that the pulmonary wedge pressure (PWP) in a group of patients with abnormally large O / C was significantly higher (17.5_ 5.3 mm Hg, mean __ 1 SD) than in a group without large O / C (13.5 +_ 3 mm Hg, P < .001). Fuller et a143 found O / C to be inversely proportional to radionuclear EF (r = -.81) using single measurements in a group of 15 patients with suspected or proven heart disease. They also calculated a multiple regression equation relating
dZ/dt
l\ AT
ECG
\./ 0 wave
Fig 2. First time derivative of impedance waveform (dZ/dt) and ECG is shown to demonstrate the following features: C wave (maximum acceleration of blood during ventricular systole), O wave (occurs during passive ventricular filling), and AT (time from start of mechanical systole to the point of maximum acceleration of blood during systole),
IMPEDENCE CARDIOGRAPHY FOR LV FUNCTION
C/Tz and O / C to radionuclear E F and obtained better correlation with radionuclear E F (r = .87) than with either C/Tz or O / C alone. Therefore, it would appear that the height of the O wave relative to the height of the C wave is at least a semiquantitative measure of ventricular function. More evaluation is required to better define this relationship. ACCELERATION INDEX
A single study46 has examined the validity of yet another index thought to reflect ventricular function, namely height of the C wave (C)/ acceleration time (AT; see Fig 2). These investigators performed impedance cardiography on 29 patients with chest pain but with insignificant coronary artery stenoses (group 1), on 21 patients with high-grade coronary artery stenosis and mild to moderate shortness of breath on exertion (group 2), and on 30 healthy controls (group 3). The mean acceleration index for each group was 23, 15, and 36, respectively, suggesting a lower index for patients with lower cardiac function (P < .01). Groups 1 and 2 were then subjected to exercise, and the mean acceleration index for each group increased by 250% and 198%, respectively (P < .001). Therefore, both the absolute value of this index and the response to exercise appear to differentiate at least semiquantitatively between those with good and those with poor ventricular function. THE CLINICAL USE OF VOLUME VERSUS PRESSURE FOR CARDIAC EVALUATION
The impedance calculations discussed above have all been compared with EF measured by other techniques. However, current bedside technology (the PA catheter) measures enddiastolic pressure (EDP). It is reasonable to assume that impedance may be able to provide valid estimates of both E F and SV, therefore, EDV will be able to be calculated (EDV = [SV/ EF] - SV). However, because impedance and the PA catheter do not measure the same variable, direct comparison between the methods can only be achieved if EDP and E D V are predictably related. For historical perspective, it is worth reviewing Starling's original work, 47 which found in an isolated beating heart and lung preparation, that by increasing venous
271
inflow volume and without altering afterload, there was an increase in cardiac output and, simultaneously, an increase in the volume of the heart. Therefore, this pivotal work examines the relationship between filling volume and cardiac output with pressures changing as secondary variables. This work has been confirmed by many others including Folse and Braunwald 48 who found the same relationship in a number of intact dog preparations. The relationship of E D P to E D V is variable and dependent on the compliance of the ventricle, which may alter in many diseased states. A number of studies 49-51 have simultaneously measured PWP and L V E D V (calculated from radionuclear EF and thermodilution cardiac output measurements). These studies performed in ICU patients with sepsis or heart problems, 5~ with adult respiratory distress syndrome, 51 or after coronary artery bypass surgery, 49 have failed to show a predictable relationship between the PWP and LVEDV. This lack of a relationship is almost certainly because of the variability of LV compliance observed in the critically ill and is probably responsible for the observed lack of a relationship between thoracic impedance and PWP. 15 Therefore, it can be seen that, in a number of situations, E D P cannot reliably predict EDV. From the original work on hemodynamics, it would appear that the primary variable of interest is E D V and that, although there is use for measures of EDP, a measure of E D V should provide better information as to the functional state of the heart. SUMMARY
There are a number of different methods by which the impedance waveform can at least partly predict ventricular function. Of these methods, the measurement of systolic time intervals has been best validated. However, much work still needs to be done on a wide variety of ICU and non-ICU patients to validate a stable and predictable relationship between P E P / V E T and EF. Further work may also validate the other indices discussed above, but less confidence can be expressed as to their eventual clinical use at present. All of the work to date has examined the
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HUGH D. FULLER
relationship between impedance and LV function. Although the impedance tracing is known to largely reflect LV ejection and aortic root flow,52 there may be some contribution from right ventricular function. To further evaluate this contribution, work using first-pass radio-
nuclear techniques to selectively look at right ventricular EF will need to be done. ACKNOWLEDGMENT
I would like to thank Debbie Keay for typing the manuscript.
REFERENCES
1. Swan HJC, Ganz W, Forrester JS, et al: Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. N Engl J Med 283:447-451, 1970 2. Gore JM, Goldberg RJ, Spodick DH, et al: A community-wide assessment of the use of pulmonary artery catheters in patients with acute myocardial infarction. Chest 92:721-727, 1987 3. Robin ED: The cult of the swan ganz catheter. Ann Intern Med 103:445-449, 1985 4. Robin ED: Death by pulmonary artery flow-directed catheter. Chest 92:727-731, 1987 5. Knaus WA, Draper EA, Wagner DP, et al: An evaluation of outcome from intensive care in major medical centres. Ann Intern Med 104:410-418, 1986 6. Guyatt GH, Ontario Intensive Care Study Group: A randomised controlled trial of right heart catheterisation in critically ill patients. J Intens Care Med 6:91-95, 1991 7. Fein AM, Goldberg SK, Walkenstein MD, et al: Is pulmonary artery catheterization necessary for the diagnosis of pulmonary edema? Am Rev Respir Dis 129:10061009, 1984 8. Rowley KM, Clubb KS, Walker-Smith GJ, et al: Right-sided infective endocarditis as a consequence of flow-directed pulmonary-artery catheterization. N Engl J Med 311:1152-1156, 1984 9. Sprung CL, Jacobs LJ, Caralis PV, et al: Ventricular arrhythmias during Swan-Ganz catheterization of the critically ill. Chest 79:413-415, 1981 10. Spring CL, Pozen RG, Rozanski JJ, et al: Advanced ventricular arrhythmias during bedside pulmonary artery catheterization. Am J Med 72:203-208, 1982 11. Connors AF, Castele R J, Farhat NZ, et al: Complications of right heart catheterization: A prospective autopsy study. Chest 88:567-572, 1985 12. Kubicek WG, Patterson RP, Witsoe DA: Impedance cardiography as a noninvasive method of monitoring cardiac function and other parameters of the cardiovascular system. Ann NY Acad Sci 170:724-732, 1970 13. Secher NJ, Thomsen A, Arnsbo P: Measurement of rapid changes in cardiac stroke volume. An evaluation of the impedance cardiography method. Acta Anaesthesiol Scand 21:353-358, 1977 14. Goldstein DS, Cannon RO, Zimlichman R, et al: Clinical evaluation of impedance cardiography. Clin Physiol 6:235-251, 1986 15. Donovan KD, Dobb G J, Woods WPD, et al: Comparison of transthoracic electrical impedance and thermodilution methods for measuring cardiac output. Crit Care Med 14:1038-1044, 1986 16. Judy WV, Powner DJ, Parr K, et al: Comparison of electrical impedance and thermal dilution measured car-
diac output in the critical care setting. Crit Care Med 13:305, 1985 (abstr) 17. Bernstein DP: Continuous noninvasive real time monitoring of stroke volume and cardiac output by thoracic electrical bioimpedance. Crit Care Med 14:898-901, 1986 18. Appel PL, Kram HB, Mackabee J, et al: Comparison of measurements of cardiac output by bioimpedance and thermodilution in severely ill surgical patients. Crit Care Med 14:933-935, 1986 19. Bernstein DP: Continuous non invasive real time monitoring of cardiac output by thoracic electrical bioimpedance. Crit Care Med 13:355, 1985 (abstr) 20. Shoemaker WC, Appel PL, Kram HB, et al: Multicomponent noninvasive physiologic monitoring of circulatory function. Crit Care Med 16:482-490, 1988 21. Spinale FG, Reines HD, Crawford FA: Comparison of bioimpedance and thermodilution methods for determining cardiac output: Experimental and clinical studies. Ann Thorac Surg 45:421-425, 1988 22. Salandin V, Zussa C, Risica G, et al: Comparison of cardiac output estimation by thoracic electrical bioimpedance, thermodilution, and tick methods. Crit Care Med 16:1157-1158, 1988 23. Gotshall RW, Wood VC, Miles DS: Comparison of two impedance cardiographic techniques for measuring cardiac output. Ann Biomed Eng 17:495-505, 1989 24. Castor G, Molter G, Helms J, et al: Determination of cardiac output during positive end-expiratory pressure-Noninvasive electrical bioimpedance compared with standard thermodilution. Crit Care Med 18:544-546, 1990 25. Sullivan PJ, Martineau RJ, Hull KA, et al: Comparison of bioimpedance and thermodilution measurements of cardiac output during aortic surgery. Can J Anaesth 37:$78, 1990 (abstr) 26. Northridge DB, Findlay IN, Wilson J, et al: Noninvasive determination of cardiac output by Doppler echocardiography and electrical bioimpedance. Br Heart J 63:93-97, 1990 27. Fuller HD: Accuracy of cardiac output (CO) determination by impedance cardiography (IC): A meta-analysis. Clin Invest Med 13:B18, 1990 (abstr) 28. Garrard CL, Weissler AM, Dodge HT: The relationship of alterations in systolic time intervals to ejection fraction in patients with cardiac disease. Circulation 52:455462, 1970 29. Capan LM, Bernstein DP, Patel KP, et ah Measurement of ejection fraction by bioimpedance method. Crit Care Med 15:402, 1987 (abstr) 30. Appel PL, Bernstein DP, Curtis DL, et al: Evaluation of a continuous, on line, real time non invasive cardiac output and ejection fraction measurement by electrical
IMPEDENCE CARDIOGRAPHY FOR LV FUNCTION
bioimpedance in critically ill patients. Crit Care Med 15:364, 1987 (abstr) 31. Hanna L, Lopez-Majano V, Ward J, et al: Noninvasive ejection fraction monitoring: A comparison of the impedance method to the radionuclide cardiography. Anaesthesia 69:A308, 1988 (Abstr) 32. Hill DW, Merrifield A J: Left ventricular ejection and the heather index measured by non invasive methods during postural changes in man. Acta Anaesthesiol Scand 20:313320, 1976 33. Linde M, Ohnhaus EE, Kirch W: Mechano- and impedance cardiography parameters in patients with heart failure in administration of a calcium antagonist. Z Kardiol 78:181-186, 1989 34. Linde M, Ohnhaus EE, Kirch W: The heather index in impedance cardiography. Int J Cardiol 19:387-388, 1988 35. Smith JJ, Muzi M, Barney JA, et al: Impedancederived cardiac indicies in supine and upright exercise. Ann Biomed Eng 17:507-515, 1989 36. Heather LW: A comparison of cardiac output values by the impedance cardiograph and dye dilution techniques in cardiac patients. National Aeronautics and Space Administration CR.10 N70-10015:247-258, 1969 37. Hubbard WN, Fish DR, McBrien DJ: The use of impedance cardiography in heart failure. Int J Cardiol 12:71-79, 1986 38. Richards NT, McBrien D J: Changes in the impedance cardiogram occurring with change in posture in patients with heart disease. Int J Cardiol 20:365-372, 1988 39. Celsi A, Imperatori A, Soffiantino F: Riproducibilita delle misure di impedenza elettrica toracica. G Ital Cardiol 16:573-577, 1989 40. Judy WV, Demeter RJ, Toth PD: Fluid challenge assessment by bioelectrical impedance. Crit Care Med 14:379, 1986 (abstr) 41. Judy WV, Hall JJ, Elliott WC: Left ventricular ejection fraction measured by the impedance cardiographic method. Federation Proceedings 42:1006, 1983 (abstr) 42. Miles DS, Gotshall RW, Quinones JD, et al: Imped-
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ance cardiography fails to measure accurately left ventricular ejection fraction. Crit Care Med 18:221-228, 1990 43. Fuller HD, Turpie F, Raskob G, et al: Validity of ejection fraction determination by impedance cardiography. Clin Invest Med 14:A22, 1991 (suppl A, abstract) 44. Lababidi Z, Ehmke DA, Durnin RE, et al: The first derivative thoracic impedance cardiogram: A useful signal for timing events in the cardiac cycle. National Aeronautics and Space Administration CR.10 N70-10009:142-161, 1969 45. Gabriel S, Oro L: The effect of posture on the first derivative thoracic impedance cardiogram in patients with myocardial infarction. Acta Med Scand 198:219-221, 1975 46. Feng S, Okuda N, Fujinami T, et al: Detection of impaired left ventricular function in coronary artery disease with acceleration index in the first derivative of the transthoracic impedance change. Aviat Space Environ Med 11:843847, 1988 47. Starling EH: The Linacre Lecture on the Law of the Heart. London, UK, Longmans, Green & Co, Ltd., 1918, pp 1-27 48. Folse R, Braunwald E: Determination of fraction of left ventricular volume ejected per beat and of ventricular end-diastolic and residual volumes. Circulation 25:674-685, 1962 49. Ellis R J, Mangano DT, VanDyke DC: Relationship of wedge pressure to end-diastolic volume in patients undergoing myocardial revascularization. J Thorac Cardiovasc Surg 78:605-613, 1979 50. Calvin JE, Driedger AA, Sibbald W J: Does the pulmonary capillary wedge pressure predict left ventricular preload in critically ill patients. Crit Care Med 9:437-443, 1981 51. Sibbald WJ, Driedger AA, Myers ML, et al: Biventricular function in the adult respiratory distress syndrome: Haemodynamic and radionuclide assessment, with special emphasis on right ventricular function. Chest 84:126-134, 1983 52. Geddes LA, Baker LE: Thoracic impedance changes following saline injection into right and left ventricles. J Appl Physiol 33:278-281, 1972
Cardiovascular Diseases VOL XXXVI, NO 4
JANUARY/FEBRUARY 1994
Evaluation of Left Ventricular Function by Impedance Cardiography: A Review Hugh D. Fuller
VER THE PAST 20 years the bedside measurement of ventricular function has become a standard in the critically ill because of the development of the pulmonary artery (PA) catheter. 1 Despite this development, there is, to date, conflicting evidence and opinion as to the benefit to patients of this maneuver, 2-6and it has a low but important risk of major morbidity and mortality.7-n Although it may not be possible to reach a solid conclusion as to the overall benefit of the PA catheter, the same information accurately and reliably collected by a noninvasive technique (without risk from adverse side effects) would be more acceptable because of its more favorable risk-benefit ratio. Impedance cardiography~2 is a noninvasive technique that measures the impedance of a low-current, high-frequency alternating current across the thorax. From measured changes in thoracic impedance associated with the cardiac cycle, calculation of stroke volume (SV) and cardiac output can been made and has been shown to correlate moderately well with concurrently measured thermodilution cardiac output. 13-27It has also been suggested that measurements from thoracic impedance tracings may predict various markers of ventricular function. If this is true, then impedance cardiography may be able to provide as much hemodynamic information as the PA catheter and may make use of the PA catheter unnecessary in many cases. The remainder of this review will discuss the data relating to impedance prediction of ventricular function. Studies reviewed here were sought by an extensive MEDLINE search (from 1966 to present) of articles relating to impedance cardiography and ventricular function, ejection fraction
O
(EF), end-distolic volume (EDV), and systolic time intervals. In addition, studies cited by other articles were sought, and reports in the advertising literature distributed by impedance cardiograph manufacturers were also reviewed. Finally, reports from contracts sponsored by the National Aeronautics and Space Administration (Houston, TX) were obtained and reviewed. In this way, a complete review of the existing literature was obtained. SYSTOLIC TIME INTERVALS
It has been established that in hearts with reduced ventricular function the ratio of the preejection period to ventricular ejection time (PEP/VET) is increased. Garrard et aF s confirmed this, finding a good negative correlation between PEP/VET, calculated from electrocardiogram (ECG) and aortic pressure tracings, and radionuclear EF measurements (r = -.90). Using a combination of ECG and impedance tracings (see Fig 1), both PEP and VET can be calculated, allowing prediction of ventricular function by impedance. A number of studies have examined the relationship between impedance-calculated PEP/VET and radionuclear measurements of EF. Capan et a129 reported results from 26 patients with ischemic or myopathic heart disease who underwent simultaneous impedance From the Department of Medicine and the Regional Critical Care Program, McMaster University, Hamilton, Ontario, Canada. Address reprint requests to Hugh D. Fuller, MB, MSc, FRCPC, Department of Medicine, St Joseph's Hospital, 50 Charhon Ave E, Hamilton, Ontario, Canada, L8N 4A6. Copyright 9 1994 by W.B. Saunders Company 0033-0620/94/3604-000155.00/0
Progress in Cardiovascular Diseases, Vol XXXVI, No 4 (January/February), 1994: pp 267-273
267
268
HUGH D. FULLER
dZ/dt
/ A wave q-Z
PEP
ECG
and gated-pooled scans. A linear relationship between the two techniques was established, and a moderately good negative correlation (r = - . 8 5 ) was found. The equation derived from this relationship was then used to predict EF by impedance. Using Capan's equation for calculation of impedance EF, Appel et aP ~ reported on 32 intensive care unit (ICU) patients, who underwent simultaneous impedance and gated-pooled scans. The results show correlation to be only fair when EF was greater than 40% (r = .7) and to be very poor when EF was lower. Hanna et aP 1 studied 17 volunteers who did not have heart disease before undergoing minor surgical procedures. Two were excluded because of ventricular ectopy, and single paired readings of impedance and radionuclear EF were performed on remaining volunteers. There was good correlation between impedance and gated-pooled EF (r -- .90), but poorer correlation between impedance and first-pass radionuclear EF (r = .77). However, the impedance EF for the first-pass studies was calculated from 16 consecutive heart beats, whereas the firstpass radionuclear EF involves only 4 or 5 beats per ventricle. Therefore, this discrepancy may account for the poorer correlation with first pass. From these studies, there appears to be moderately good validity of impedance PEP/ VET for prediction of left ventricular EF (LVEF) although it may be less accurate in critically ill patients. 3~ Studies examining the response of PEP/VET to various maneuvers were also reviewed. Hill et
Fig 1. First time derivative of impedance waveform (dZ/dt) and ECG are shown to demonstrate the following features: systolic time intervals (PEP and VET), C wave (maximum acceleration of blood during ventricular systole), A wave (caused by atrial systole), Tz (the sum of C wave height and A wave height), and q-Z (the interval from the start of electrical ventricular systole to the point of maximum acceleration of blood during systole).
aP 2 performed head-up and head-down tilts in a well-constructed study. The investigators used five normal volunteers, who maintained each position for 5 minutes before measurement and returned to supine baseline between postural changes. Impedance PEP/VET decreased by 12.1% in the head-down position, because of increased cardiac filling and output, and increased by 61.5% in the head-up position, because of reduced cardiac filling and output. Linde et a133,34performed a double-blind crossover study of the calcium blocker Nisoldipine in patients with congestive heart failure (CHF). A reduction in impedance PEP/VET was observed as a result of an increase in ventricular function while taking Nisoldipine. Smith et a135 measured impedance PEP/VET in six volunteers at rest and at two levels of exercise. The PEP/VET was reduced on exercise (P < .05) because of the increase of cardiac output and EF. Therefore, there is good evidence that impedance PEP/VET responds appropriately to maneuvers that produce clinically significant change. THE HEATHER INDEX
In 1969, Heather suggested a new index of cardiac function based on the impedance tracing. 36 He made impedance recordings on 14 patients undergoing cardiac catheterization, 7 of whom had valvular problems. He calculated the ratio of C wave height to the time to peak of C wave, C/(q - Z), (see Fig 1) and found that
IMPEDENCE CARDIOGRAPHY FOR LV FUNCTION
in a group of 4 patients with New York Heart Association (NYHA) grade III-IV functional capacity, this index was markedly lower than in those with N Y H A grade I or II (P = .001). A number of sources support the accuracy of this index. Hubbard et aP 7 performed impedance recordings on 37 patients with a clinical diagnosis of CHF. The Heather index was low in all of these patients, but this was a descriptive study and did not mention absolute levels nor did it compare readings with those in patients without heart failure. Richards et a138 made impedance recordings on 74 patients with a variety of heart diseases (but no functional capacity was recorded) and on 22 normal volunteers. Recordings were made in the supine position followed by sitting and then standing, but without return to the supine baseline. The Heather index in the normal volunteers decreased from supine to sitting position, presumably because of reduction in cardiac output, but this decrease was not significant. In the supine position, the patients had Heather indexes significantly lower than those for the normal volunteers (P < .05); however, the values increased significantly for patients but not for volunteers (P < .05) on transferring from the supine to sitting position. A semiquantitative subgroup analysis of the patient group showed that those patients taking vasodilators (presumably those with more severe disease) had the greatest reduction when in the supine position and had the greatest response to postural change. Therefore, this study shows an expected reduction in the Heather index in patients with heart disease that is likely to be greatest in those with more severe disease, presumably because of reduced cardiac function. The response to change from the supine to sitting position is to be expected on the basis of off-loading an overloaded left ventricle through this postural maneuver. The degree of benefit from this maneuver is likely to be greatest in those with the worst heart function. Better quantification of cardiac function in the patient group would have allowed more confidence in this interpretation. Two other studies also showed response of the Heather index to change. Linde et a133,34 showed an increase in the Heather index after Nisoldipine administration to subjects with heart disease, presumably caused by off-loading of
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overloaded ventricles. Smith et a135 also showed an increase of 26% (not statistically significant) after steady-state exercise. Correlation of the Heather index with impedance P E P / V E T was performed by Hill et a132in five healthy subjects. Impedance recordings were made repeatedly after 5 minutes in each of the following positions: supine, head-down 30 ~, supine, head-up 40 ~ and supine. A total of 100 paired measurements were made, and a correlation coefficient of 0.79 was found between P E P / V E T and the Heather index. A study by Celsi et a139measured reliability by calculating the Heather index from impedance recordings taken twice in the same day on 10 normal subjects. The coefficient of variation for this value was acceptable at 14.5%. Therefore, these studies show that the Heather index has moderate validity as a measure of ventricular function and shows moderate reliability and good responsiveness to clinically significant change. CONTRIBUTION OF A WAVE HEIGHT
Judy et al 4~ have suggested that C/Tz from the first time derivative of the impedance tracing (see Fig 1) predicts EF and have published two abstracts in support of this claim. In the first abstract, 4~ impedance EF was calculated in 15 hypovolemic ICU patients subjected to a fluid challenge of 1,200 mL. EF decreased by 2.4% +_ 0.5% (SEM) as the wedge pressure increased 9 -+ 0.8 mm Hg. No further details are given, and the only conclusion that can be made is that this measurement responds to fluid challenge similar to EF, in a situation that produced an expected increase in wedge pressure. The second abstract 41 compared impedance and firstpass radionuclear EF in 493 patients in sinus rhythm with normal valve function. He divided the subjects into three groups, those with normal function, those with ischemia, and those with heart failure, but did not further define these groups. The mean and standard deviation of impedance EF was very close to that of radionuclear EF (formal statistical analysis was not applied), but there was very little difference between the mean EF in the three groups (64.8%, 49.7%, and 58.7%, respectively); therefore, little can be inferred from such a narrow range of values.
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Although these two abstracts suggest that C/Tz may at least in part reflect EF, there are two theoretical concerns regarding its validity. First, its calculation requires the presence of an A wave (associated with atrial contraction) in the impedance tracing. Many critically ill patients are in atrial fibrillation; therefore, accurate calculation using this method will not be possible in these patients. Second, EF represents the ratio of ejected volume to total diastolic volume of blood, but the impedance calculation represents a ratio of accelerations rather than volumes. Therefore, intuitively it would appear not to have a solid theoretical base, thus making it less likely to be a valid calculation. Miles et aP e more recently compared impedance EF (calculated as C/Tz) with radionuclear EF in 95 patients with a variety of cardiovascular and other diseases, 7 of whom had unspecified arrhythmias. However, the techniques were not measured simultaneously, and the correlation between the two techniques was poor (r = - . 0 4 ) . Somewhat better correlation was observed by Fuller et al, 43 however, using single measurements in 15 patients with suspected or proven heart disease, 12 in sinus rhythm, and 3 in atrial fibrillation. Concurrent measurement of impedance tracing and radionuclear EF gave a correlation between C/Tz and EF of r = .51, still not adequate for clinical prediction of EF. Therefore, it would appear that on both theoretical and experimental grounds, C/Tz is unlikely to be a valid indicator of true EF.
HEIGHT OF THE O WAVE
The O wave (see Fig 2) is a small upward deflection in the first time derivative of the impedance waveform, occurring in midcardiac cycle. Lababidi et a144 found in 10 patients with mitral stenosis that the O wave peak occurred coincident with or within 0.01 second of the opening snap. Therefore, it is reasonable to assume that the O wave represents passive blood flow from atrium to ventricle during diastole. The presence of an enlarged O wave has been noted by several investigators 37,45 in patients with evidence of CHF. In some of these patients, particularly those with more severe disease, the enlarged O wave is present at all times. In others it is normal when supine but becomes enlarged in the head-down and legselevated positions, which is presumably caused by increased cardiac filling that worsens the degree of ventricular dysfunction. Calculation of the ratio of O wave height to C wave height (O/C; see Fig 2) was said by Donovan et a115 to be abnormal if it exceeded 0.3. He found that the pulmonary wedge pressure (PWP) in a group of patients with abnormally large O / C was significantly higher (17.5_ 5.3 mm Hg, mean __ 1 SD) than in a group without large O / C (13.5 +_ 3 mm Hg, P < .001). Fuller et a143 found O / C to be inversely proportional to radionuclear EF (r = -.81) using single measurements in a group of 15 patients with suspected or proven heart disease. They also calculated a multiple regression equation relating
dZ/dt
l\ AT
ECG
\./ 0 wave
Fig 2. First time derivative of impedance waveform (dZ/dt) and ECG is shown to demonstrate the following features: C wave (maximum acceleration of blood during ventricular systole), O wave (occurs during passive ventricular filling), and AT (time from start of mechanical systole to the point of maximum acceleration of blood during systole),
IMPEDENCE CARDIOGRAPHY FOR LV FUNCTION
C/Tz and O / C to radionuclear E F and obtained better correlation with radionuclear E F (r = .87) than with either C/Tz or O / C alone. Therefore, it would appear that the height of the O wave relative to the height of the C wave is at least a semiquantitative measure of ventricular function. More evaluation is required to better define this relationship. ACCELERATION INDEX
A single study46 has examined the validity of yet another index thought to reflect ventricular function, namely height of the C wave (C)/ acceleration time (AT; see Fig 2). These investigators performed impedance cardiography on 29 patients with chest pain but with insignificant coronary artery stenoses (group 1), on 21 patients with high-grade coronary artery stenosis and mild to moderate shortness of breath on exertion (group 2), and on 30 healthy controls (group 3). The mean acceleration index for each group was 23, 15, and 36, respectively, suggesting a lower index for patients with lower cardiac function (P < .01). Groups 1 and 2 were then subjected to exercise, and the mean acceleration index for each group increased by 250% and 198%, respectively (P < .001). Therefore, both the absolute value of this index and the response to exercise appear to differentiate at least semiquantitatively between those with good and those with poor ventricular function. THE CLINICAL USE OF VOLUME VERSUS PRESSURE FOR CARDIAC EVALUATION
The impedance calculations discussed above have all been compared with EF measured by other techniques. However, current bedside technology (the PA catheter) measures enddiastolic pressure (EDP). It is reasonable to assume that impedance may be able to provide valid estimates of both E F and SV, therefore, EDV will be able to be calculated (EDV = [SV/ EF] - SV). However, because impedance and the PA catheter do not measure the same variable, direct comparison between the methods can only be achieved if EDP and E D V are predictably related. For historical perspective, it is worth reviewing Starling's original work, 47 which found in an isolated beating heart and lung preparation, that by increasing venous
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inflow volume and without altering afterload, there was an increase in cardiac output and, simultaneously, an increase in the volume of the heart. Therefore, this pivotal work examines the relationship between filling volume and cardiac output with pressures changing as secondary variables. This work has been confirmed by many others including Folse and Braunwald 48 who found the same relationship in a number of intact dog preparations. The relationship of E D P to E D V is variable and dependent on the compliance of the ventricle, which may alter in many diseased states. A number of studies 49-51 have simultaneously measured PWP and L V E D V (calculated from radionuclear EF and thermodilution cardiac output measurements). These studies performed in ICU patients with sepsis or heart problems, 5~ with adult respiratory distress syndrome, 51 or after coronary artery bypass surgery, 49 have failed to show a predictable relationship between the PWP and LVEDV. This lack of a relationship is almost certainly because of the variability of LV compliance observed in the critically ill and is probably responsible for the observed lack of a relationship between thoracic impedance and PWP. 15 Therefore, it can be seen that, in a number of situations, E D P cannot reliably predict EDV. From the original work on hemodynamics, it would appear that the primary variable of interest is E D V and that, although there is use for measures of EDP, a measure of E D V should provide better information as to the functional state of the heart. SUMMARY
There are a number of different methods by which the impedance waveform can at least partly predict ventricular function. Of these methods, the measurement of systolic time intervals has been best validated. However, much work still needs to be done on a wide variety of ICU and non-ICU patients to validate a stable and predictable relationship between P E P / V E T and EF. Further work may also validate the other indices discussed above, but less confidence can be expressed as to their eventual clinical use at present. All of the work to date has examined the
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relationship between impedance and LV function. Although the impedance tracing is known to largely reflect LV ejection and aortic root flow,52 there may be some contribution from right ventricular function. To further evaluate this contribution, work using first-pass radio-
nuclear techniques to selectively look at right ventricular EF will need to be done. ACKNOWLEDGMENT
I would like to thank Debbie Keay for typing the manuscript.
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IMPEDENCE CARDIOGRAPHY FOR LV FUNCTION
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