II) VALIDATIONS

Clinical studies in PDF format are available in the download section of this website.

As a cardiac output measuring system, PhysioFlow^TM is validated against generally accepted reference methods, such as "direct" Fick, thermodilution and Echo-Doppler. Validations have been obtained at rest and during exercise on cyclo-ergometer, on healthy subjects and patients suffering from cardiac or pulmonary diseases. Reproducibility has also been tested thoroughly.

1) Reproducibility

1st test

Results : excellent reproducibility (r = 0.98 p < 0.0001)

2nd test

Similar results were obtained during another test :

Results : excellent inter- intra-operator reproducibility (r > 0.96, p<0.0001)

It has also been shown that reproducibility is remarkable during cyclo-ergometer exercise, and under non-optimal measurement conditions (important modifications of electrode positions).

2) Validation against "direct" Fick method (Eur 5 Appl Physiol(2000) 82: 313-320)

Exercise by a new impedance cardiography device: comparison with the "direct" Fick method

Anne CHARLOUX, MD, Eve LONSDORFER-WOLF, MD, Eliane LAMPERT, MD, PhD, Monique OSWALD-MAMMOSSER, MD, Bertrand METTAUER, MD, PhD, Bernard GENY, MD, PhD, and Jean LONSDORFER, MD. Service des Explorations Fonctionnelles Respiratoires, Cardio-Circulatoires et de l'Exercice, Hôpitaux Universitaires de Strasbourg, Hôpital Civil, BP 426, 67091 Strasbourg Cedex, France.

Study objectives : To evaluate the reliability and accuracy of a new impedance cardiography device, the PhysioFlow^TM, at rest and during a mild constant effort performed in the supine position.

Design : We compared cardiac output determined simultaneously by two methods, the PhysioFlow^TM and the "direct" Fick methods.

Patients : Forty patients referred for right cardiac catheterization, 14 with sleep apnoea syndrome and 26 with chronic obstructive pulmonary disease. All patients had normal left ventricular function.

Measurements and results : Thirty two patients have been able to perform an exercise, ranging from 10 to 50 watts, 53% of patients pedaling at a 30 W workrate. The 72 cardiac outputs measured at rest and during exercise range from 4.34 to 14.84 L/min for Physio Flow and from 3.60 to 15.03 L/min for "direct" Fick. VO2 range from 0.14 to 1.19 L/min. Regression of QcPF (L/min) against VO2 (L/min) is shown in fig 2. The regression equation, based on 72 measurements, is QcPF = 7.2 O2 + 4.2. Individual values of cardiac output obtained concomitantly by the two methods (QcFick and QcPF) are plotted in fig 1. The correlation coefficient was 0.89 (p<0.001) for resting values and 0.85 (p<0.001) for exercising values. There was no difference between cardiac output means measured by the two methods, either at rest (mean QcPF = 6.25 ±± 1.14 L/min, mean QcFICK = 6.32 ±± 1.42 L/min, NS) or during exercise (mean QcPF = 9.89 ±± 2.17 L/min, mean QcFICK = 10.15 ±± 2.35 L/min, NS).

Comparison of the two techniques with the Bland and Altmann method is represented in fig 2. At rest, the mean difference (QcFICK-QcPF) was 0.07 L/min (95% confidence interval: -0.23, +0.27 L/min), which represents 0.29% of the mean resting cardiac output. The (QcFICK-QcPF) difference did not vary significantly with the mean of (QcFICK, QcPF). The limits of agreement are (-1.18, +1.32 L/min) at rest. Thus, in 95% of paired measurements, the difference between QcFICK and QcPF is within a (-19%, +19%) interval. During a mild effort, the mean of the (QcFICK-QcPF) difference is 0.26 L/min (2.44% of mean exercising cardiac output) with a (-0.17 , +0.69 L/min) 95% confidence interval. The limits of agreement during exercise are -2.16 and +2.68 L/min (-21%, +26% of cardiac output). In all patients, the direction of the changes in impedance cardiography values always corresponded to those measured with "direct" Fick. At rest, QcFICK and QcPF differed by 20% or more in only one patient among the 40 (2.5%). During exercise, two (QcFICK-QcPF) differences among the 32 measurements are equal or are greater than 20% (6.2%).

Conclusions : Physio Flow provides a clinically acceptable evaluation of cardiac output in these conditions. This new impedancemetry device deserves further study in other populations and situations.

Fig1 : Correlation graphs : At rest (n = 40)

Fig2 : Bland and Altmann scattergrams : Exercise (n = 32)

3) Validation against Echo-Doppler

Use of new thoracic impedance method to assess cardiac index in children

(Published at the American Society of Anesthesiology, Scientific Sessions, Orlando 1998)

E Wodey, MD, X Beneux, MD, F Carre, MD, O Azzis, MD, C Ecoffey, MD. Depts of Anesthesiology 2 and Physiology , Hôpital Pontchaillou, 35033 Rennes, France.

Introduction: Measurements of cardiac output give important information about hemodynamic status, and it can be evaluated by several methods. In 1966 Kubicek et al described a method of calculating stroke volume, i.e. cardiac output, from the thoracic impedance signal. However, special electrodes, specific configuration, skin cleansing, and measurements for estimation of one cylinder or truncated cone model, were essential to obtain the true value of stroke volume, but they could also induce some error in this assessment. Recently a new thoracic impedance method Physio Flow® (Manatec Biomedical, Macheren, Paris) has been available. Unlike traditional impedance methods, positioning of electrodes is not critical, nor are special eletrodes or skin cleansing. In addition, no estimation of cylinder or truncated cone model is needed. Thus, the aim of this study was to evaluate the ability of Physio Flow® to determine cardiac index in healthy children.

Methods: Cardiac index measurements were performed in 24 healthy children (median age 11, range 6-16 yrs) in a double-blind manner by echocardiography-Doppler Sonos 1000™ (Hewlett-Packard, Andover), and by Physio Flow™ in a supine position at rest. In all cases informed parental consent was obtained. Aortic annular diameter (Øao) and flow velocity in the ascending aorta were measured. Cardiac Index (CIdop) was calculated from the volumetric equation: CIdop (L.min-1.m-2) = Vao (cm.sec-1) x (pix(FIao x 0.5)2)(cm2) x 0.06 / BSA (m2). Concerning the new bioimpedance thoracic method, six standard electrodes were applied on children without specific skin preparation, provided that one pair was at the thorax base and another was at the thorax apex. Measured parameter were maximum rate of change of transthoracic impedance (dZ/dtmax) and the thoracic fluid inversion time (TFIT). According to the manufacturer, there was a linear relationship between the following combined parameters: stroke volume/(BSA x pulse pressure) and TFIT/heart rate, allowing estimation of the calibration stroke volume. After calibration, stroke volume varied according to the variations of TFIT and dZ/dtmax. Spearman's rank test was used for the correlation studies.

Results : Cardiac index quantified by continuous wave Doppler (CIdop) was significantly linked to cardiac index quantified by PhysioFlow^TM(CIimp) (Figure A). An underestimation of cardiac index was obtained by the PhysioFlow^TM method for all measurements. The overall bias between CIdop and CIimp was +1.28 L.min-1.m-2. The 95% limits of agreement between both methods was ±0.96 L.min-1.m-2 (Figure B).

Discussion: CI may be measured with reliability from PhysioFlow^TM in healthy children older than 6 years of age at rest, although systematic under-estimation was found. Reference: Kubicek WG et al :Aerospace Med 1966 ;37 :1208-1212

4) Detection of coronary artery disease during cyclo-ergometer exercise, using new generation impedance cardiography (*)

(*) This abstract displays results that will be thoroughly analyzed and published later

Objectives:

The protocol was designed to determine if a new non-invasive cardiac output measuring device, called PhysioFlow^TM, based on analysis of instantaneous thoracic impedance variations (new generation impedance cardiography ICG), could be helpful to detect Coronary Artery Disease (CAD) during cyclo-ergometer exercise.

We have used the following criteria for positivity of ICG during cyclo-ergometer exercise (figure 1) : stroke volume profile (SV) alteration : SV decreases at a certain level of effort after having increased, whereas heart rate continues to increase. The result is that at the end of exercise, SV is not maximal.

Methods:

1) Patients

Heart rate and stroke volume determinations were performed during cyclo-ergometer exercise on a group of 31 patients, as well as simultaneous exercise ECG. These patients were referred to our unit because of various clinical symptoms (chest pain, dyspnea). All patients were measured whatever their morphology, age, or sex . All patients who represented positive cyclo-ergometer exercise or clinical symptoms (chest pain and / or dyspnea) have undergone control coronary angiography (19 men, 12 women, age = 58 years ±10 years).

2) Materials

Exercise ECG : Quinton 5000 series.

The ICG method (PhysioFlow^TM ) is a new impedance method based on analysis of instant thoracic impedance variations, using six electrodes (two for ECG (measurement of heart rate) and four for ICG). Measured parameters are heart rate (HR), contractility index (CI), and Thoracic Flow Inversion Time (TFIT) (active period of left ventricular ejection). (SV) is derived from CI and TFIT. Cardiac Output (CO) = HR x SV.

3) Procedures

Patients underwent a classical cyclo-ergometer exercise in the same hospital cardiology unit, with steps of 30 watts every 2 minutes. ICG was calibrated just before exercise started, and recorded measurements every 12 heart beats (mean value of 12 previous beats). Exercise was stopped when patients displayed clinical signs of CAD, pain, dyspnea, or ECG ST-segment depression.

We performed control coronary angiography, as it is considered the gold standard for this study.

Results:

Discussion:

Only one patient had positive control coronary angiography and negative ICG and ECG examination, because he had only 40% stenosis of the right coronary artery and was receiving betablocker treatment, making it difficult to detect CAD during exercise. In the remaining cases (30), (where EKG, ICG, and control coronary angiography were all positive), stroke volume profile alteration always occurred before EKG ST-segment depression.

Overall, EKG was not consistent with control coronary angiography 8 times out of 31, and ICG only one time in 31. In 2 more cases the EKG could not be interpreted because of conduction defects (ICG and control coronary angiography were both positive in these cases).

Conclusion:

Considering these results, stroke volume profile measurements performed by ICG seem to be a useful tool in association with EKG for detecting CAD during cyclo-ergometer exercises. They help making a decision concerning control coronary angiography prescription, especially when EKG gives a negative or unclear conclusion. It is also useful to assess hemodynamic impairments when related to CAD and in the setting in of heart failure or other diseases like Syndrome X (when simple control coronary angiography cannot show micro circulation abnormality).

Figure 1 : Normal and abnormal stroke volume profile (before/after dilatation)

5) Other results :

Reference method : Echography - Doppler

Reference method : VO2 and CO2 rebreathing

III) CASE STUDIES (REAL PATIENTS)

The Hemodynamic Cross

Case n°1 : Cardiac insufficiency