Bioimpedance-derived differences in cardiac physiology during exercise stress testing in low-risk chest pain patients.
Objective: The objectives are to show that there are different cardiac physiologic responses to exercise stress test in Chest Pain Evaluation Unit patients with and without true CAD that could be used to stratify patients and that there is a sex difference in TEB results.
Methods: Patients 18 to 65 years of age with low-risk chest pain were eligible. Patients were attached to the TEB throughout the exercise stress test procedure. Heart rate (HR) was monitored. Primary dependent variables were TEB-measured cardiac output (CO, L/min) and stroke volume (SV, ml) at peak exercise. Secondary variables were TEB-measured ejection fraction (%), end-diastolic volume (EDV, ml), ventricular ejection time (ms), and thoracic fluid index ([OMEGA]) at peak exercise. Outcome variables were either proved CAD or patient sex. CAD was proved by angiography, stress scintigraphy, or stress echocardiogram. Results were compared using a Student's t test assuming equal variances, with significance considered at a P < 0.05, and 95% confidence intervals were calculated for significant results.
Results: Nine patients had proved CAD, 82 patients did not. Forty-three women and 48 men were included in the study. At peak exercise, patients with CAD had a significantly smaller increase in EDV than patients without CAD (32.8 [+ or -] 59.5 ml versus 89.3 [+ or -] 101.8 ml) without a significant change in CO, SV, or HR. At peak exercise, women had a significantly smaller increase in CO and SV without a significant change in HR. In addition, women had a significantly smaller increase in EDV.
Conclusion: When compared with patients without CAD, patients with CAD have a significantly smaller increase in EDV and a trend toward the same effect in CO and SV. Women have significantly smaller increases CO, SV, and EDV compared with men. Because there were no differences in HR, using HR as the sole end point would miss these differences. TEB is a practical means of measuring these variables.
Key Words: cardiac output, cardiography, impedance, monitoring
Cardiac output (CO) measurement by thermodilution and dye-dilution is invasive, carries the potential for significant complications, and is not practical in the outpatient setting. In contrast, thoracic electrical bioimpedance (TEB) is simple, noninvasive, and without risk to the patient. Because it uses a hands-off approach, it has better intermeasurement and interobserver reliability than thermodilution. (1) As the reliability and validity become better defined, TEB is finding an expanded role in many areas of medicine. Among its uses are defining changes in seriously ill patients, (2-10) monitoring pregnancy, (11-18) evaluating the effects of environmental stressors on healthy individuals, (19-25) and assessing drug effects. (26), (27)
Sex-related differences in chest pain management have been well documented. Not only is there a documented sex difference in demographics of chest pain, but there is also a documented sex difference in chest pain detection and evaluation. This difference has led to underdiagnosis of heart disease in women when signs and symptoms alone are considered. The addition of cardiac physiologic information could increase the yield of true-positive stress test results in female patients. (28-38) There is a need to better identify women at high cardiac risk. (36)
The use of TEB in outpatients has only been evaluated in a few studies, (39-44) despite the fact that this would be an excellent modality for use in these environments. There is usually insufficient time to initiate invasive monitoring in outpatient cases, nurses often are not trained in the technique, and the equipment is not readily available. There is a strong body of literature emerging, which indicates that TEB may be an effective method of tracking cardiac physiologic changes during exercise testing.
The ability to recognize low-risk patients with chest pain has led to alternatives to conventional coronary care for this group, including reduced time in coronary care units, direct admission to a step-down unit, and management in short-stay observation units. We presently use a Chest Pain Evaluation Unit (CPEU) composed of a specialized physician-staffed unit, which provides care to patients with chest pain, whose electrocardiograms (ECGs) and initial cardiac injury markers are not diagnostic for ischemia. Our previous study demonstrated that nearly 90% of patients initially identified as low risk by clinical assessment can be safely discharged from the emergency department on the basis of the results of the exercise test. (45), (46)
In this study we evaluate chest pain patients who are at low risk for acute coronary syndromes. We searched for ischemia-and sex-related differences in TEB-obtained cardiac physiologic variables. The hypotheses for this study are the following: 1) There are different cardiac physiologic responses to exercise stress testing (EST) in CPEU patients with and without true coronary artery disease (CAD) that could be used to stratify patients, and 2) there are sex-related differences in cardiac physiologic responses to EST.
A convenience sample of patients 18 to 65 years of age undergoing EST was included. For the evaluation of chest pain patients we used our previously described eligibility criteria and exercise treadmill testing protocol. (45), (47) Patients underwent EST according to a Bruce or modified Bruce protocol depending on physician discretion. We enrolled these patients during a 6-month period. Patients were simultaneously attached to the TEB monitor while being connected to the exercise ECG monitor. TEB monitoring did not preclude or interfere with the standard exercise ECG monitoring. Patients were included if data were obtained by TEB. Patients were excluded if they were unwilling or unable to consent, or if they were [beta]-blocked. End point measurements for EST were 85% maximum predicted heart rate (HR) or symptoms, such as shortness of breath or chest pain. The study was approved by the institutional review board to conform to standard practice for research in humans. Written informed consent was obtained from all participants.
The primary dependent variables were TEB-derived CO and stroke volume (SV) at rest and the change in variables between rest and peak exercise. Secondary variables were thoracic fluid index, ventricular ejection time, ejection fraction (EF), and end-diastolic volume (EDV) as determined by TEB during EST. We monitored HR because this was used for end point decisions in EST testing. In addition we calculated cardiac index as CO divided by weight, and systemic vascular resistance with the formula CO times 80 divided by mean arterial pressure.
The outcome variable was a true-positive CAD on the basis of one of the following; 1) coronary angiography (positive is a >50% reduction in coronary artery lumen diameter), 2) myocardial stress (exercise or pharmacologic) scintigraphy by single-photon emission computed tomography (positive is stress-induced perfusion defect), or 3) stress (dobutamine or exercise) echocardiography (positive is stress-induced segmental wall motion abnormality).
Two subgroup analyses were also performed. A first subgroup analysis was performed looking for sex-related differences. A second subgroup analysis looked at only nonnegative EST using a decision tree analysis to determine cutoff points that could be used to stratify patients.
The NCCOM3-R7 (Bomed Corp., Irving, CA) monitor was used to obtain the impedance data. The electrodes are applied on the lateral neck and flank bilaterally. Two leads generate a low electrical field across the thorax using 2.5 mA alternating current at 70 KHz while the other two sensing leads measure changes in voltage. These sensing electrodes reflect changes in impedance and also function as ECG leads to enable the machine to monitor HR (needed to express the SV as CO).
Sex, body weight (kg), and height (cm) are entered into the TEB monitor. Derived cardiac variables are then displayed on the monitor. These include SV, CO, HR, EF, left ventricular ejection fraction, and EDV. Data were collected with the monitor in slow mode, during which the device provides an average result for the six variables on 16 consecutive accepted beats.
An a priori power calculation showed that 15 patients per group were needed to show a difference of 50% in primary physiologic variables with a power of 80%. Results were downloaded from the TEB monitor into a palmtop computer, transferred into an Excel database (Microsoft Corp., Redmond, WA), and analyzed with the use of the SPSS 9.0 statistical software package (SPSS, Inc., Chicago, IL). A P < 0.05 was considered significant, and 95% confidence intervals were calculated on all significant differences. Answer Tree software (SPSS, Inc.) was used to create a decision tree based on the data.
One hundred twenty-eight patients were tested. Data were obtainable in 94 of these patients. Thirty-four had the device applied but did not produce acceptable readings. No patients with initial TEB readings needed to be excluded later because of motion artifact. Three patients were excluded because of their use of [beta]-blockers, leaving 91 people who were entered in the study.
Normal values, baseline values, and increases from baseline are outlined in Table 1. Twenty-one patients had non-negative EST results. Nine patients (10%) had proved CAD and nonnegative EST results. Forty-three women and 48 men were entered in the study. At peak exercise the CAD-positive patients had no significant changes over baseline for the primary variables CO and SV, although there was a trend toward a smaller increase in those variables. Among the secondary variables, CAD-positive patients had a significantly smaller increase in EDV. These results are summarized in Table 2.
Figure 1 shows the results of the decision tree analysis on the data for patients with nonnegative EST, indicating that either CO or EDV could effectively stratify all but one of the CAD-positive patients. At peak exercise, women had significantly smaller increases in CO and SV. Among the secondary variables, women had significantly smaller increases in EDV and cardiac index. They also had a significantly smaller decrease in systemic vascular resistance. These results are also summarized in Table 2. No significant results were found when both sex and pressure of CAD were taken into account. Figure 1 illustrates a decision tree analysis of the data using an increase in CO of less than 12.0 L/min or an increase in EDV of less than 55 ml as the decision variables. As can be seen, the negative group contained 1 (11%) of 9 positives while the positive group was 8 (67%) of 12 positives. The positive predictive value and sensitivity of this rule is 89% (8 of 9; Fig. 1). Figure 2 illustrates a typical curve of CO and HR as collected over time from the TEB monitor during an EST. The x axis represents time, and the y axis represents the measured HR or CO, respectively.
The first important finding in this study was that reproducible TEB results were obtained despite the motion artifact that occurred during an EST. In fact, there was little effect of motion on the results. Significant, important differences were observed between both the CAD and the sex subgroups. Between the CAD-positive and CAD-negative patients, only the change in EDV was significantly different. However, between men and women there were more significant differences, including the primary variables (CO and SV), one of the secondary variables (EDV), and the calculated variables (systemic vascular resistance and cardiac index). Of note, there were no significant differences in either subgroup in the change in HR, which is in agreement with the fact that the HR was used (as was expected) as the primary end point for the
* When patients with known coronary artery disease are compared with those without disease, exercise stress testing increases all variables to the same degree at peak exercise except end-diastolic volume.
* When women are compared with men, the increase in heart rate at peak exercise is the same.
* Women have significantly smaller increases in cardiac output and stroke volume at peak exercise.
* Heart rate may lead to unequal end points in women and men during exercise stress testing and may therefore lead to incorrect conclusions. EST. EDV proved to be one of the best variables (followed closely by CO) for differentiating these groups as shown in the decision tree analysis. The fact that there was a significant sex difference in changes in CO suggests that HR may not be the best end point to use for an EST. The increase in CO during the EST in men was almost twice that seen in women and may account for the lower published rates of positive testing in women when HR is used as the end point.
Sex-related differences in the management of patients with chest pain have been well documented. Not only is there a clear sex difference in the demographics of these patients, but also there is a sex-related difference in the sensitivity and specificity of the diagnostic tests used in their evaluation. This difference has led to underdiagnosis of heart disease in women when signs and symptoms alone are considered. An unacceptably high rate of false positives occurs if only the results of EST are used. The addition of cardiac physiologic information could increase the positive predictive value of the test, particularly in female patients. (28-38)
[FIGURE 1 OMITTED]
No previous study has attempted to stratify TEB results by sex. Previous studies have looked at the use of TEB during exercise in normal volunteers and in patients with ischemic heart disease. (48), (49) Measurements were made by TEB during exercise (21), (48-57) and during postural stress. (24), (25), (58) When these studies compared the TEB results with those of other standard measurements, there were high correlation coefficients (for CO, r = 0.96 and 0.90, respectively). The conclusion is that the value of TEB was in evaluating trends in results, and changes with exercise or position rather than the absolute values of cardiac variables. Although CO, thoracic fluid index, and ventricular ejection time have all been suggested in the past as correlating with true ischemic heart disease, no previous study has evaluated the role of these markers in a prospective manner.
[FIGURE 2 OMITTED]
Our chest pain service evaluates 1,100 people per year, of which half qualify for EST. The positive stress test rate of this population is 15%; however, false-positives account for half of these, which can lead to additional testing and higher costs. (47) The addition of TEB may result in better recognition of true-positive ESTs and lead to a decrease in cost and fewer follow-up tests. (45) This is the first report looking at the use of this modality in emergency department patients.
We were able to show that TEB is a good noninvasive method of monitoring cardiac physiologic variables. There are numerous reasons a good noninvasive tool for the measurement of CO is desirable for use with chest pain patients undergoing EST. It provides moment-to-moment physiologic information about the patient and clarifies patient status changes that may not be apparent using other monitoring techniques. CO measurement by thermodilution or dye dilution is not practical in this setting. (55), (56) Also, because TEB uses a hands-off approach, it has better intermeasurement and interobserver reliability than the invasive monitoring techniques. The ability to further stratify the nonnegative EST results was of particular importance to us in the practical management of these patients. Because false-negative results are so rare, only the nonnegative results need to be stratified. As can be seen from our results, there were small differences between the groups. When dichotomous statistical methods were used, it was possible to separate the two groups to a reasonable extent on the basis of CO alone. This method needs to be applied in the context of a much larger test group.
Previous studies have suggested that TEB monitoring was useful in quantifying changes in cardiac variables during early treatment of congestive heart failure, trauma, and neurologic problems. (39), (40), (43), (59), (60) We think that the addition of TEB monitoring may help clarify the results of routine exercise electrocardiography and direct the clinician in the management of patients with chest pain suggestive of myocardial ischemia.
Limitations of the Study and Future Research Directions
This study has limitations. First, the patients were entered as a convenience sampling. This may have led to a selection bias on the basis of times of the day that the investigator was available. Thirty-four patients had no data recorded. Some reasons were because the body habitus prevented proper application of the leads, the process of applying electrodes interfered with standard patient care, or the monitor did not record any data. This suggests that approximately 27% of patients will not produce adequate data for TEB analysis. We found, however, that many of the patients with large body habitus were able to have the pads applied and had appropriate information recorded. We could not predict ahead of time which patients would or would not be candidates for monitoring.
The monitor that we used was an older model. The NCCOM-R7 has been under continuous improvement and is presently available under a different name from a different company. The newer machines use algorithms that are reported by the companies as more accurate although there is no present literature to support this claim. Use of this machine, however, demonstrates its usefulness in this setting. This is not an outcome study. We were able to determine that all patients survived at 3 months; however, future studies need to focus not only on this sex difference but also on the sex differences among patients with positive stress test results.
Future direction for the use of TEB in a research capacity would be to evaluate EST results in light of long-term follow-up information regarding morbidity and mortality in patients with an initial presentation of chest pain. It would also be of value in double-blind evaluations of early management approaches to other medical and surgical patients.
God has not called me to be successful; God has called me to be faithful.
Table 1. Results at baseline and increases over baseline for all variables measured (a) Normal mean baseline values Primary outcome variables CO (L/min) 6.0 [+ or -] 2.0 SV (ml/min) 80 [+ or -] 16 Secondary outcome variables EDV (ml) 120 [+ or -] 50 EF (%) 45 [+ or -] 10 TFI (Ohms) 29 [+ or -] 9 Information for calculated variables MAP (mm Hg) 90 [+ or -] 20 HR (beats/min) 80 [+ or -] 20 Calculated variables SVR (dynes*sec/c[m.sup.3]) 1,600 [+ or -] 400 CI (L/min/kg) 95 [+ or -] 19 Mean baseline Primary outcome variables CO (L/min) 6.6 [+ or -] 2.2 SV (ml/min) 80.0 [+ or -] 25.4 Secondary outcome variables EDV (ml) 159.4 [+ or -] 56.2 EF (%) 50.2 [+ or -] 7.4 TFI (Ohms) 35.2 [+ or -] 6.7 Information for calculated variables MAP (mm Hg) 95.9 [+ or -] 2.4 HR (beats/min) 79.7 [+ or -] 2.9 Calculated variables SVR (dynes*sec/c[m.sup.3]) 1,257.6 [+ or -] 370.6 CI (L/min/kg) 81.9 [+ or -] 28.7 Increase over baseline at peak exercise (%) Primary outcome variables CO (L/min) 12.7 [+ or -] 9.4 SV (ml/min) 56.7 [+ or -] 50.1 Secondary outcome variables EDV (ml) 83.7 [+ or -] 99.7 EF (%) 7.6 [+ or -] 9.0 TFI (Ohms) -0.4 [+ or -] 2.1 Information for calculated variables MAP (mm Hg) 10.7 [+ or -] 13.4 HR (beats/min) 60.4 [+ or -] 21.3 Calculated variables SVR (dynes*sec/c[m.sup.3]) -686.9 [+ or -] 372.2 CI (L/min/kg) 153.0 [+ or -] 102.1 (a) CO, cardiac output; SV, stroke volume; EDV, end-diastolic volume; EF, ejection fraction; TFI, thoracic fluid index; MAP, mean arterial pressure; HR, heart rate; SVR, systemic vascular resistance; CI, cardiac index. Table 2. Increases over baseline for subgroup analysis of confirmed coronary artery disease-positive versus coronary artery disease-negative patients and females versus males (a) CAD-negative (n = 82) Primary outcome variables CO 13.1 [+ or -] 9.4 SV 59.3 [+ or -] 50.3 Secondary outcome variables EDV 89.3 [+ or -] 101.8 EF 7.6 [+ or -] 9.2 TFI -0.4 [+ or -] 2.2 Information for calculated variables MAP 10.9 [+ or -] 13.8 HR 60.0 [+ or -] 21.5 Calculated variables SVR -709.4 [+ or -] 335.0 Cardiac index 158.3 [+ or -] 103.0 CAD-positive P difference (n = 9) (95% CI) Primary outcome variables CO 9.1 [+ or -] 9.3 0.26 SV 33.3 [+ or -] 44.6 0.13 Secondary outcome variables EDV 32.8 [+ or -] 59.5 0.03 56.5 (7.6-105.5) (b) EF 7.7 [+ or -] 7.5 0.96 TFI -0.6 [+ or -] 0.8 0.58 Information for calculated variables MAP 9.3 [+ or -] 8.9 0.63 HR 63.4 [+ or -] 20.1 0.65 Calculated variables SVR -482.0 [+ or -] 608.5 0.30 Cardiac index 104.1 [+ or -] 82.4 0.10 Mean increase over baseline Females (n = 43) Primary outcome variables CO 8.4 [+ or -] 4.7 SV 33.4 [+ or -] 24.7 Secondary outcome variables EDV 40.8 [+ or -] 50.5 EF 8.8 [+ or -] 0.0 TFI -0.6 [+ or -] 2.2 Information for calculated variables MAP 10.1 [+ or -] 12.0 HR 56.8 [+ or -] 22.5 Calculated variables SVR -595.3 [+ or -] 394.0 Cardiac index 114.6 [+ or -] 68.6 Mean increase over baseline Males (n = 48) Primary outcome variables CO 16.5 [+ or -] 14.7 SV 77.7 [+ or -] 57.6 Secondary outcome variables EDV 122.2 [+ or -] 116.4 EF 6.5 [+ or -] 8.0 TFI -0.3 [+ or -] 2.0 Information for calculated variables MAP 11.3 [+ or -] 14.7 HR 63.5 [+ or -] 19.8 Calculated variables SVR -769.0 [+ or -] 334.7 Cardiac index 187.3 [+ or -] 114.9 P difference (95% CI) Primary outcome variables CO <0.01 8.1 (4.5-11.6) (b) SV <0.01 44.3 (25.4-63.1) (b) Secondary outcome variables EDV <0.01 81.4 (43.3-119.5) (b) EF 0.22 TFI 0.48 Information for calculated variables MAP 0.69 HR 0.14 Calculated variables SVR 0.03 173.6 (21.8-325.5) (b) Cardiac index <0.01 72.7 (32.7-112.7) (b) (a) CAD, coronary artery disease; CI, confidence interval; CO, cardiac output; SV, stroke volume; EDV, end-diastolic volume; EF, ejection fraction; TFI, thoracic fluid index; MAP, mean arterial pressure; HR, heart rate; SVR, systemic vascular resistance. (b) Significant difference.
From the Division of Emergency Medicine, Department of Internal Medicine, School of Medicine, University of California, Davis, and UC Davis Medical Center, Sacramento, CA.
This study was supported by a grant from the UC Davis Research Committee.
Reprint requests to Steven J. Weiss, MD, Division of Emergency Medicine, Department of Internal Medicine, University of California, Davis, 2315 Stockton Blvd., PSSB 2100, Sacramento, CA 95817. Email: email@example.com
Accepted October 28, 2002.
Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9611-1121
1. Bernstein DP. Noninvasive cardiac output measurement, in Grenvik A, Ayres SM, Holbrook PR, Shoemaker WC (eds): Textbook of Critical Care. Philadelphia, W.B. Saunders Co., 1989, ed 2, pp 159-185.
2. Thangathurai D, Charbonnet C, Roessler P, Wo CC, Mikhail M, Yoahida R, et al. Continuous intraoperative noninvasive cardiac output monitoring using a new thoracic bioimpedance device. J Cardiothorac Vasc Anesth 1997;11:440-444.
3. Weiss S, Calloway E, Cairo J, Granger W, Winslow J. Comparison of cardiac output measurements by thermodilution and thoracic electrical bioimpedance in critically ill versus non-critically ill patients. Am J Emerg Med 1995;13:626-631.
4. Young JD, McQuillan P. Comparison of thoracic electrical bioimpedance and thermodilution for the measurement of cardiac index in patients with severe sepsis. Br J Anaesth 1993;70:58-62.
5. Nakatsuka M, MacLeod AD. Hemodynamic and respiratory effects of transtracheal high-frequency jet ventilation during difficult intubation. J Clin Anesth 1992;4:321-324.
6. Mattar JA, Shoemaker WC, Diament D, Lomar A, Lopes AC, De Freitas E, et al. Systolic and diastolic time intervals in the critically ill patient. Crit Care Med 1991;19:1382-1386.
7. Castor G, Molter G, Helms J, Niedermark I, Altmayer P. Determination of cardiac output during positive end-expiratory pressure: Noninvasive electrical bioimpedance compared with standard thermodilution. Crit Care Med 1990;18:544-546.
8. Gotshall RW, Wood VC, Miles DS. Modified head-up tilt test for orthostatic challenge of critically ill patients. Crit Care Med 1989;17:1156-1158.
9. Preiser JC, Daper A, Parquier JN, Contempre B, Vincent JL. Transthoracic electrical bioimpedance versus thermodilution technique for cardiac output measurement during mechanical ventilation. Intensive Care Med 1989;15:221-223.
10. Appel PL, Kram HB, Mackabee J, Fleming AW, Shoemaker WC. Comparison of measurements of cardiac output by bioimpedance and thermodilution in severely ill surgical patients. Crit Care Med 1986;14:933-935.
11. Scardo J, Kiser R, Dillon A, Brost B, Newman R. Hemodynamic comparison of mild and severe preeclampsia: Concept of stroke systemic vascular resistance index. J Matern Fetal Med 1996;5:268-272.
12. Scardo JA, Vermillion ST, Hogg BB, Newman RB. Hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies. Am J Obstet Gynecol 1996;175:336-340.
13. van Oppen AC, van der Tweel I, Alsbach GP, Heethaar RM, Bruinse HW. A longitudinal study of maternal hemodynamics during normal pregnancy. Obstet Gynecol 1996;88:40-46.
14. Hobel CJ, Castro L, Rosen D, Greenspoon JS, Nessim S. The effect of thigh-length support stockings on the hemodynamic response to ambulation in pregnancy. Am J Obstet Gynecol 1996;174:1734-1741.
15. Ouzounian JG, Masaki DI, Abboud TK, Greenspoon JS. Systemic vascular resistance index determined by thoracic electrical bioimpedance predicts the risk for maternal hypotension during regional anesthesia for cesarean delivery. Am J Obstet Gynecol 1996;174:1019-1025.
16. Scardo JA, Hogg BB, Newman RB. Favorable hemodynamic effects of magnesium sulfate in preeclampsia. Am J Obstet Gynecol 1995;173:1249-1253.
17. van Oppen AC, van der Tweel I, Duvekot JJ, Bruinse HW. Use of cardiac index in pregnancy: Is it justified? Am J Obstet Gynecol 1995;173:923-928.
18. Heethaar RM, van Oppen AC, Ottenhoff FA, Brouwer FA, Bruinse HW. Thoracic electrical bioimpedance: Suitable for monitoring stroke volume during pregnancy? Eur J Obstet Gynecol Reprod Biol 1995;58:183-190.
19. Metry G, Wikstrom B, Linde T, Danielson BG. Gender and age differences in transthoracic bioimpedance. Acta Physiol Scand 1997;161:171-175.
20. van Oppen AC, van der Tweel I, Bruinse HW. Reproducibility of estimated cardiovascular function by transthoracic bioimpedance cardiography in healthy volunteers. Int J Biomed Comput 1994;37:15-18.
21. Moore R, Sansores R, Guimond V, Abboud R. Evaluation of cardiac output by thoracic electrical bioimpedance during exercise in normal subjects. Chest 1992;102:448-455.
22. Huang KC, Stoddard M, Tsueda KA, Heine MF, Thomas MH, White M, et al. Stroke volume measurements by electrical bioimpedance and echocardiography in healthy volunteers. Crit Care Med 1990;18:1274-1278.
23. Concu A, Scorcu M, Marcello C, Rocchitta A, Molari A, Esposito A, et al. Unchanging cardiac activity while increasing respiratory activity at the start of exercise in man: A beat-by-beat analysis by means of the impedance cardiography method. Cardiologia 1990;35:845-850.
24. Wong DH, O'Connor D, Tremper KK, Zaccari J, Thompson P, Hill D, Changes in cardiac output after acute blood loss and position change in man. Crit Care Med 1989;17:979-983.
25. Wong DH, Tremper KK, Zaccari J, Hajduczek J, Konchigeri HN, Hufstedler SM. Acute cardiovascular response to passive leg raising. Crit Care Med 1988;16:123-125.
26. Waluga M, Janusz M, Karpel E, Hartleb M, Nowak A. Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women. Clin Physiol 1998;18:69-76.
27. Massidda B, Fenu MA, Ionta MT, Tronci M, Foddi MR, Montaldo C, et al. Early detection of the anthracycline-induced cardiotoxicity: A non-invasive haemodynamic study. Anticancer Res 1997;17:663-668.
28. Raine RA, Crayford TJ, Chan KL, Chambers JB. Gender differences in the treatment of patients with acute myocardial ischemia and infarction in England. Int J Technol Assess Health Care 1999;15:136-146.
29. Roger VL, Jacobsen SJ, Pellikka PA, Miller TD, Bailey KR, Gersh BJ. Gender differences in use of stress testing and coronary heart disease mortality: A population-based study in Olmsted County, Minnesota. J Am Coll Cardiol 1998;32:345-352.
30. Frishman WH, Gomberg-Maitland M, Hirsch H, Catanese J, FuriaPalazzo S, Mueller H, et al. Differences between male and female patients with regard to baseline demographics and clinical outcomes in the Asymptomatic Cardiac Ischemia Pilot (ACIP) Trial. Clin Cardiol 1998;21:184-190.
31. Kosmas CE, Mallozzi M, Moten M, Banka VS. Clinical symptomatology of coronary artery disease and results of exercise thallium scintigraphy: Gender-related differences. Indian Heart J 1997;49:497-501.
32. Travin MI, Duca MD, Kline GM, Herman SD, Demus DD, Heller GV, Relation of gender to physician use of test results and to the prognostic value of stress technetium 99m sestamibi myocardial single-photon emission computed tomography scintigraphy. Am Heart J 1997;134:73-82.
33. Lauer MS, Pashkow FJ, Snader CE, Harvey SA, Thomas JD, Marwick TH. Gender and referral for coronary angiography after treadmill thallium testing. Am J Cardiol 1996;78:278-283.
34. Merz CN, Moriel M, Rozanski A, Klein J, Berman DS. Gender-related differences in exercise ventricular function among healthy subjects and patients. Am Heart J 1996;131:704-709.
35. Bergelson BA, Tommaso CL. Gender differences in clinical evaluation and triage in coronary artery disease. Chest 1995;108:1510-1513.
36. Hachamovitch R, Berman DS, Kiat H, Bairey-Merz N, Cohen I, Cabico JA, et al. Gender-related differences in clinical management after exercise nuclear testing. J Am Coll Cardiol 1995;26:1457-1464.
37. Okin PM, Kligfield P. Gender-specific criteria and performance of the exercise electrocardiogram. Circulation 1995;92:1209-1216.
38. Cerqueira MD. Diagnostic testing strategies for coronary artery disease: Special issues related to gender. Am J Cardiol 1995;75:52D-60D.
39. Velmahos GC, Wo CC, Demetriades D, Bishop MH, Shoemaker WC. Invasive and noninvasive hemodynamic monitoring of patients with cerebrovascular accidents. West J Med 1998;169:17-22.
40. Weiss SJ, Kulik JP, Calloway E. Bioimpedance cardiac output measurements in patients with presumed congestive heart failure. Acad Emerg Med 1997;4:568-573.
41. Shoemaker WC, Belzberg H, Wo CC, Milzman DP, Pasquale MD, Baga L, et al. Multicenter study of noninvasive monitoring systems as alternatives to invasive monitoring of acutely ill emergency patients. Chest 1998;114:1643-1652.
42. Shoemaker WC, Wo CC, Demetriades D, Belzberg H, Asensio JA, Cornwell EE, et al. Early physiologic patterns in acute illness and accidents: Toward a concept of circulatory dysfunction and shock based on invasive and noninvasive hemodynamic monitoring. New Horiz 1996;4:395-412.
43. Bishop MH, Shoemaker WC, Shuleshko J, Wo CC. Noninvasive cardiac index monitoring in gunshot wound victims. Acad Emerg Med 1996;3:682-688.
44. Saunders CE. The use of transthoracic electrical bioimpedance in assessing thoracic fluid status in emergency department patients. Am J Emerg Med 1988;6:337-340.
45. Kirk JD, Turnipseed S, Lewis WR, Amsterdam EA. Evaluation of chest pain in low-risk patients presenting to the emergency department: The role of immediate exercise testing. Ann Emerg Med 1998;32:1-7.
46. Farkouh ME, Smars PA, Reeder GS, Zinsmeister AR, Evans RW, Meloy TD, et al. A clinical trial of a chest-pain observation unit for patients with unstable angina: Chest Pain Evaluation in the Emergency Room (CHEER) Investigators. N Engl J Med 1998;339:1882-1888.
47. Lewis WR, Amsterdam EA, Turnipseed S, Kirk JD. Immediate exercise testing of low risk patients with known coronary artery disease presenting to the emergency department with chest pain. J Am Coll Cardiol 1999;33:1843-1847.
48. Miles DS, Cox MH, Verde TJ, Gotshall RW. Application of impedance cardiography during exercise. Biol Psychol 1993;36:119-129.
49. Sheps DS, Petrovick ML, Kizakevich PN, Wolfe C, Craige E. Continuous noninvasive monitoring of left ventricular function during exercise by thoracic impedance cardiography-automated derivation of systolic time intervals. Am Heart J 1982;103:519-524.
50. Wilson MF, Sung BH, Pincomb GA, Lovallo WR. Simultaneous measurement of stroke volume by impedance cardiography and nuclear ventriculography: Comparisons at rest and exercise. Ann Biomed Eng 1989;17:475-482.
51. Denniston JC, Maher JT, Reeves JT, Cruz JC, Cymerman A, Grover RF. Measurement of cardiac output by electrical impedance at rest and during exercise. J Appl Physiol 1976;40:91-95.
52. Hanel B, Teunissen I, Rabol A. Warberg J, Secher NH. Restricted post-exercise pulmonary diffusion capacity and central blood volume depletion. J Appl Physiol 1997;83:11-17.
53. Kim SY, Hinkamp TJ, Jacobs WR, Lichtenberg RC, Posniak H, Pifarre R. Effect of an inelastic aortic synthetic vascular graft on exercise hemodynamics. Ann Thorac Surg 1995;59:981-989.
54. Kizakevich PN, Teague SM, Nissman DB, Jochem WJ, Niclou R, Sharma MK. Comparative measures of systolic ejection during treadmill exercise by impedance cardiography and Doppler echocardiography. Biol Psychol 1993;36:51-61.
55. Smith JJ, Muzi M, Barney JA, Ceschi J, Hayes J, Ebert TJ. Impedance-derived cardiac indices in supine and upright exercise. Ann Biomed Eng 1989;17:507-515.
56. Balasubramanian V, Hoon RS. Changes in transthoracic electrical impedance during submaximal treadmill exercise in patients with ischemic heart disease: A preliminary report. Am Heart J 1976;91:43-49.
57. Seguro C, Sau F, Zedda N, Mura O, Montaldo C, Scano G, et al. Hemodynamic assessment at rest and during dynamic physical exercise in young subjects with and without hypertensive parents [in Italian]. Cardiologia 1995;40:391-397.
58. Smith JJ, Bush JE, Wiedmeier VT, Tristani FE. Application of impedance cardiography to study of postural stress. J Appl Physiol 1970;29:133-137.
59. Asensio JA, Demetriades D, Berne TV, Shoemaker WC. Invasive and noninvasive monitoring for early recognition and treatment of shock in high-risk trauma and surgical patients. Surg Clin North Am 1996;76:985-997.
60. Velmahos GC, Wo CC, Demetriades D, Shoemaker WC. Early continuous noninvasive haemodynamic monitoring after severe blunt trauma. Injury 1999;30:209-214.
Steven J. Weiss, MD, Amy A. Ernst, MD, Gary Godorov, MD, Deborah B. Diercks, MD, Josh Jergenson, BS, and J. Douglas Kirk, MD