Literature Supporting SMX Diagnostic Applications

Zo and Differential Diagnosis of Acute Exacerbation of Heart Failure

Milzman D, Moskowitz L Samaddar R, et al (Providence Hosp,Georgetown Univ)
The utility of thoracic impedance to evaluate chest radiograph changes from acute heart failure patients in the Emergency Department. J Cardiac Failure 1998; 4:Supp 1, 37.
    Admission Zo (IQ™) and chest xrays were compared 176 patients presenting to the ED with presumed heart failure. Significant differences in mean Zo (ohms) were reported between xrays of patients with alveolar edema (Zo 14.5), interstitial edema (Zo 18.0), cephalization (Zo 20.8) and normal chest xray (Zo 25.6). A Zo of < 19 ohms had a 90% sensitivity and 94% specificity for identifiying heart failure on chest xray. Conclusion: Zo accurately predicts the presence and severity of acute pulmonary edema in heart failure patients.

Milzman D, Hogan C, Han C, et al 
Continuous, noninvasive cardiac output monitoring quantifies acute congestive heart failure in the ED. Crit Care Med 1997;25:A47.
    ICG (IQ™), chest X ray, and Forrester (1977) HF subset classification were used to classify 114 HF patients on admission to ED. Zo < 19 had 90% sensitivity and 94% specificity for identifying pulmonary edema on chest X ray. X ray  and Zo correlates: Alveolar edema 14.8 ohms; interstitial edema 18.5 ohms; cephalization 22.2 ohms; normal 23.1 ohms. Conclusion: ICG identifies HF patients with critically low CI and accurately quantifies pulmonary edema.

Milzman D, Hogan C, Han C, et al
Continuous, non-invasive cardiac output monitoring quantifies severity of congestive heart failure in the emergency department. Acad Emerg Med 1996;3:064.

Prediction of Extracellular Water Volume

Armstrong LE, Kenefick R, Castellani J, et al (U Conn)
Bioimpedance spectroscopy technique: Intra-, extracellular, and total body water. Medicine and Science in Sports and Exercise 1997; 29:1657-1663.

Patel RV, Peterson E, Silverman N, Zarowitz B (Henry Ford Hosp)
Estimation of total body and extracellular water in post-coronary artery bypass graft surgical patients using single and multiple frequency bioimpedance. Crit Care Med 1996; 24:1824-1828.

Tatara T, Tsuzaki K (Tokyo)
Segmental bioelectrical impedance analysis improves the prediction for extracellular water volume changes during abdominal surgery. Crit Care Med 1998; 26:470-476.

ACI for Determination of Rejection of Cardiac Transplantation

Weinhold C, Reichenspurner H, Fulle P, et al (Munich)
Registration of thoracic electrical bioimpedance for early diagnosis of rejection after heart transplantation. J Heart Lung Transplant 1993; 12:8320836.
    Endomyocardial biopsies and ICG parameters  were obtained per routine protocol in 35 heart transplant patients, 17 had acute rejection episodes diagnosed by biopsy.  Acceleration index measured by ICG was significantly lower than the baseline of patients with acute rejections, and lower than all non-rejection patient values. The mean decrease was 28%.  A 20% decrease of acceleration index from baseline had a sensitivity of 71% and specificity of 100% for cardiac transplant rejection. Conclusions: Measurement of acceleration index by ICG is a satisfactory, simple means of assessing rejection in the outpatient setting and for guiding therapy and initiating further diagnostic evaluation.

ACI for Screening Coronary Artery Disease

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. Clin Cardiol 1988; 11:843-847.

Koerner K, Borzotta A, Wilson J (Portland) 
Screening for coronary artery disease with impedance cardiography. Crit Care Med 1997;25:A47.

Utility of Evaluation of dZ/dt Waveform Abnormalities:

O:C and Pulmonary Artery Wedge Pressure

Woltjer H, Bogaard H, Bronzwaer J, et al  (Amsterdam)
Prediction of pulmonary capillary wedge pressure and assessment of stroke volume by noninvasive impedance cardiography.  Am Heart J 1997;134:450-455.
    The ICG O/C ratio (distance from X to O peak/ height of dZ/dt max) was correlated with PA wedge pressure in 24 patients, in supine position. 23 had CAD, 8 with mitral regurgitation, aortic regurgitation and/or stenosis. Over a PAWP range of 3-30 torr, correlation with O/C, r = .92. Elimination of patients with valvular dysfunction did not change the relationship. Stroke volume correlation was r = .68, when AS and AR patients eliminated (n=5), r = .87. Conclusion: ICG O/C ratio may be used to predict PAWP. 

A and O Wave Evaluation in Left Ventricular Dysfunction

Hubbard W, Fish D, McBrien D. (Nat Heart Hosp, London)
The use of impedance cardiography in heart failure. Internat J Cardiol 1986;12:71-79.
ICG  dZ/dt waveform analysis in 37 patients with documented HF and 23 patients with vague HF signs and symptoms, but normal chest X rays, showed abnormal systolic dZ/dt in all 60 patients. 36 of 37 patients with clinical evidence of HF had abnormal O waves at rest or with leg elevation. Except in severe cases the O wave diminished in size with upright positioning and vasodilator therapy. 15 of the 18 patients with no clinical signs of HF had abnormal O waves that responded to position and vasodilator therapy. Conclusion: Abnormal O waves correlate with severity of HF and are an indicator of therapeutic response.

Pickett B, Buell J (Texas Tech Univ HSC)
Usefulness of the impedance cardiogram to reflect left ventricular diastolic function. Am J Cardiol 1993;71:1099-1103.
    ICG waveforms and Doppler transmitral flow patterns were compared in 8 normal subjects and 9 patients with documented diastolic dysfunction. ICG O wave (early diastole) and A wave (late diastolic filling) and Doppler flow patterns were manipulated by position changes (supine, 30 head-up and head-down tilt). The height of O waves and depth of A waves increased in both groups in the head-down position. The ICG A wave in heart failure was significantly deeper than in normal subjects. Conclusion: Both the O wave and A wave are preload dependent. Authors postulate that large, negative A wave and Doppler E/A ratio < 1 identify reduced ventricular compliance and pulmonary venous flow reversal.

Ramos MI (trained Univ Mn, 1977 Rehab Med Boston Univ MC)
An abnormal early diastolic impedance waveform: A predictor of poor prognosis in the cardiac patient? Am Heart J 1977 94;3:274-281.
    Retrospective analysis of 81 patients with acute MI and/or severe heart failure. Thirty patients had abnormal dZ/dt waveform with an early diastolic wave in ICG tracing. 66% of this group were NYHA Class III and IV. 90% of patients with normal dZ/dt were NYHA Class I and II. Those with early diastolic wave on dZ/dt had significantly more cardiovascular complications (dysrhythmias, HF, angina, cardiac arrest) and higher mortality (50% vs 4%) than the patients with normal dZ/dt waveforms. Conclusion: Presence of early diastolic wave in dZ/dt waveform is predictive of poor functional and physiologic outcomes.

O and X Wave Evaluation in Cardiac Valvular Disease

Karnegis J, Heinz J, Kubicek W (Univ Minn)
Mitral regurgitation and characteristic changes in impedance cardiogram. Br Heart J 1981;45:542-48.
    ICG waveforms of 36 patients with mitral regurgitation (MR) were compared to 22 patients without cardiovascular disease.  An algebraic index was calculated from both the dZ/dt and  Z (Height of C + X – O waves [authors refer to O as V wave]). Patients with MR had significantly smaller dZ/dt and  Z indices than those with normal mitral valves. Following mitral valve replacement surgery, 5 patients had increased indices approaching those of the normal subjects. Conclusion: Calculation of dZ/dt and  Z indices may aid in the diagnosis of mitral regurgitation.

Schieken R, Patel M, Falsetti H, et al  (Univ Iowa)
Effect of mitral valvular regurgitation on transthoracic impedance cardiogram. Br Heart J 1981;45:166-172.
    ICG and echocardiograms recorded in 23 normal persons and 23 patients with mitral regurgitation (MR) at rest, during isometric handgrip exercise, and during amyl nitrate inhalation. Significant differences were shown between groups in the: height of the ICG O wave (early diastolic filling), mitral regurgitant fraction (= area under the O wave / area under dZ/dt + area under the O wave); Patients with MR had significantly increased area under O wave and regurgitant fraction with isometric exercise, control group had no ICG change; amyl nitrate increased the height of the dZ/dt, reduced regurgitant fraction and nonsignificantly decreased the O wave area in MR patients; mitral regurgitant fraction calculated by ICG correlated closely (r = .89) with that measured from cardiac catheterization. Conclusion: Analysis of ICG O wave and its relationship to dZ/dt may have utility in the diagnosis, evaluation of severity and response to therapy in patients with mitral regurgitation.

Schieken R, Patel M, Falsetti H, et al 
Effect of aortic valvular regurgitation upon the impedance cardiogram. Br Heart J 1978;40:958-963.
    ICG and echocardiograms recorded in 22 normal persons, 22 patients with clinical signs and symptoms of aortic regurgitation (AR) and 22 patients with AR documented by cardiac catheterization. O wave height and ratio O:dZ/dt was less in AR patients than in control group. The area above the X point (synchronous with aortic valve closure) and the ratio of area above X / area under dz/dt correlated with AR volume (r = .89) and angiographic AR fraction (r = .90) Handgrip exercise increased ICG AR fraction. Conclusion: ICG may be a sensitive measure of the severity of aortic regurgitation.

Systolic Time Intervals and Estimation of Ejection Fraction

Capan LM, Bernstein D, Patel, et al (NYU and Palomar, CA)
Measurement of ejection fraction by bioimpedance method. Crit Care Med 1987; Suppl April:402.

Bowling LS, Sagemen S, O’Conner S, et al (SanDiego Naval Hosp)
Lack of agreement between measurement of ejection fraction by impedance cardiography versus radionuclide ventriculography. Crit Care Med 1993;21:1523.

Time Intervals in Differentiation of Systolic and Diastolic Heart Failure

Mattar J, Aldrighi J, Passos H   (Brazil) 
6th World Congress Intensive and Crit Care Med, Madrid, 1993
Simultaneous assessment of left ventricular systolic and diastolic time intervals in cardiac pump failure.
    Systolic and diastolic function were evaluated in patients with stroke volume index < 30 ml/m2 using systolic and diastolic time intervals measured by ICG  patients had normal systolic and abnormal diastolic function, 8 had abnormal systolic function with normal diastolic function, and 3 had both systolic and diastolic dysfunction. Conclusion: ICG may be of use to aid differentiation of systolic and diastolic dysfunction.

Effects of dobutamine on systolic and diastolic time intervals in the critically ill patient.
    Systolic and diastolic time intervals and other hemodynamic parameters measured by ICG before and after dobutamine infusion. Increases in HR, CI, and SVI were associated with a slight shortening of systolic time interval and a more significant lengthening of diastolic time interval. Conclusion: Enhanced CI during dobutamine infusion is related to improved diastolic function as evaluated by ICG.

Mattar,  Conference/199?:
#196: A study of left ventricular compliance by the combined approach of thermodilution and electrical bioimpedance.
    A static measure of LV compliance was derived from end diastolic index/pulmonary artery wedge pressure in 16 patients. No relationship was apparent between the PA wedge pressure and end diastolic index and was reflected in a wide range of LV compliance calculations in patients with similar PA wedge pressures. Conclusion: Simultaneous assessment of PA wedge pressure and ICG parameters may enable improved identification of LV impairment and interventions.

#198: Cardiac pump failure with normal systolic function and diastolic dysfunction of the left ventricle.
Diastolic dysfunction was evaluated by the diastolic time ratio, isovolumetric relaxation period/ filling time. Normal individuals had diastolic time ratio of > 0.6. msec. Patients with cardiac failure (n=9, SVI <30) had a mean diastolic time ratio of 0.77 msec (range 0.61-1.0). Conclusion: Identification of diastolic dysfunction and therapeutic interventions may be improved ICG evaluation.

General Utility of Systolic Time Intervals 

Boudoulas H: Systolic Time Intervals. European Heart J 1990;11: Suppl 1, 93-104.
(Uses echocardiogram, phonocardiogram, carotid pulse tracing)

Evaluation of Preload Status

Larson F, Morgaensen L, Tedner B  (Sweden)
Influence of furosemide and body posture on transthoracic electrical impedance in AMI. Chest 1986;90:733-737.

Soubiran C, Harant I, De Glisezinski I, et al. (France)
Cardio-respiratory changes during the onset of head-down tilt. Aviation, Space, and Environmental Medicine 1996;67:648-653.

Wong DH, Tremper K, Zaccari, et al. (Long Beach VAMC)
Improved cardiovascular response to passive leg raising after acute blood loss. Crit Care Med 1987; April, Suppl, 402.

Kassis E: Cardiovascular response to orthostatic tilt in patients with severe congestive heart failure. Cardiovasc Research 1987; 21:362-368. (used echocardiography, not ICG)
Identification of Hemodynamic Derangement in Heart Failure    

Belardinelli R, Ciampani N, Costantini C, et al (Italy)
Comparison of impedance cardiography with thermodilution and direct Fick methods for noninvasive measurement of stroke volume and cardiac output during incremental exercise in patients with ischemic cardiomyopathy. Am J Cardiol 1996;77:1293-1301.
    ICG , Fick and thermodilution (TDCO) cardiac output was measured at rest and during cycle ergometer exercise in patients with coronary artery disease: 15 LV hypertrophy and EF < 40%; 10 normal LV size and function. Those with normal LV function had significantly greater CO and SV during exercise. ICG correlations with TDCO and Fick CO at rest and during exercise ranged from r = .85 to .98 (Bias and precision not reported). ICG measurements were also obtained a week apart demonstrating no significant differences and good reproducibility. Conclusion: ICG monitoring can provide useful information to assess the hemodynamic profile of patients with ischemic cardiomyopathy during exercise/rest and assessing serial hemodynamic changes. 

Milzman D, Moskowitz L Samaddar R, et al
Thoracic impedance monitoring of cardiac output in the ED improves heart failure resuscitation. J Cardiac Failure 1998; 4:Supp 1, 30.
    Admission ICG (IQ™) parameters, Zo, cardiac index, and stroke volume were compared to admission vital signs in 294 HF patients admitted to the ED. Patients were placed into 4 groups based on: Zo > or < 21ohms, and CI > or < 3.6 l/min/m2. There was no difference in admission vital signs between groups despite the varied hemodynamic function. 72% of patients showed improved hemodynamic values and dyspnea scores following treatment based on ICG. Conclusion: Vital signs alone are inadequate to assess and manage HF patients in the ED; ICG parameters provide objective data to classify and treat HF.

Milzman D, Battatta A, Zlidenny A, et al
Non-invasive cardiac output monitoring improves the acute resuscitation of congestive heart failure in the E.D. beyond vital signs. Crit Care Med 1998;26:A62.
    ICG (IQ™) evaluation of 87 ED HF patients with acute decompensation showed 39% with CI < 2.5, 94% with SV < 80, 76% had SVR > 1500. Low CI and SV present in 97% patients with MAP < 80 and high SVR. There was no correlation between BP and CI.  In patients with HR > 100, physician judgement was < 50 % in identifying patients with low SV and elevated SVR, and worse in patients with normal HR. Conclusion: ICG assessment can improve the evaluation and management of HF patients in the ED.

Panigrahi G, Pedersen A, Boudoulas H (VA, Denmark, Ohio State)
Hemodynamics in acute myocardial infarction: the use of impedance cardiography. J Medicine 1983;14:375-388.

Petersen J, Drabaek H, Gleerup G, et al (Denmark)
ACE Inhibition with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension. Angiology 1996;47:233-240.
    ICG (SV, CI, ACI, SVR) Doppler (A/E ratio) and echocardiography (LV mass) evaluation of 13 patients with hypertension comparing hemodynamic and LV diastolic function during treatment with placebo, hydrochlorothiazide, and spirapril. During 4 week trials of each, only A/E ratio significantly changed. Conclusion: Beneficial effect of spirapril not dependent on BP, hemodynamic variables, LV mass, or end-systolic wall stress.

Ramano M, Monteforte I, Cardei S, et al (Italy)
Cardiopulmonary exercise response in patients with left ventricular dysfunction or heart failure: a noninvasive study by gas exchange and impedance cardiography monitoring. Cardiology 1996;87:147-152.
    Exercise response of 20 HF patients (10 NYHA I, 10 NYHA II-III) was compared with 8 normal subjects by VE/VCO2 and ICG. In response to bicycle exercise, HF patients showed no change in SV or SVR, and an increased HR. Normal subjects increased SV and HR and had a decrease in SVR.  HF patients had higher VE/VCO2 compared to controls. Conclusion: Abnormal ICG hemodynamic and increased ventilatory response to exercise explains exertional dyspnea in HF patients.

Scherhag, A, Pfleger S, deMey C,  et al  (Un Heidelberg & Mannheim, Germany)
Continuous measurement of hemodynamic alterations during pharmacologic cardiovascular stress using automated impedance cardiography. J Clin Pharmacol 1997;37: 21S-28S.
    Utilized 2D echo and ICG to evaluate stress response to dobutamine (n=26) and dipyridamole (n=24) stress. In patients receiving dipyridamole, there was no significant differences in cardiac index, stroke volume index or SVRI in those with stress induced wall motion abnormalities compared to patients with negative stress echo. 13 patients in dobutamine group had stress induced wall motion abnormalities.  Increases in stroke volume and cardiac index were significantly smaller in those with wall motion abnormalities. Conclusions: ICG measured stroke volume is a mechanism to detect patients with pathophysiologic stress response. A minimum stroke volume increase of 50% had 100% sensitivity and 70% specificity; a minimum stroke volume increase of 35% had 85% sensitivity and specificity for detecting positive stress echo results.

Ventura H, Smart F, Stapleton D, et al (Tulane University Medical Center)
Reproducibility of postural hemodynamic responses by thoracic electrical bioimpedance in HF patients. J Cardiac Failure, 1998 4:Suppl 1, 31.
    ICG (IQ™)  hemodynamic parameter reproducibility in response to postural changes was tested in 5 patients with HF. Two sets of data were obtained in lying, sitting, and standing positions. Comparisons of the two sets showed no differences cardiac index, stroke volume, Zo, acceleration contractility index or heart rate, in any of the positions. Conclusion: ICG parameters are reproducible in HF patients and may be useful to assess therapeutic interventions.

Weiss S, Kulik J, Calloway E  (LSU & Vanderbilt-SW)
Bioimpedance cardiac output measurements in patients with presumed congestive heart failure. Acad Emerg Med 1997;4:568-573.
    Seven patients with clinical signs of CHF were studied using ICG  before and after diuretic and, in 2 patients, captopril. Findings described in case reports and showed varying changes in CO, SV, ACI and thoracic fluid index. SVR not measured. Conclusion: Investigators stated treatment of CHF patients in the ED should be augmented by hemodynamic monitoring and identified significant study limitations.