WO1990003145A1 - Procede et appareil de diagnostic et de traitement de l'hypertension - Google Patents

Procede et appareil de diagnostic et de traitement de l'hypertension Download PDF

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Publication number
WO1990003145A1
WO1990003145A1 PCT/US1989/003613 US8903613W WO9003145A1 WO 1990003145 A1 WO1990003145 A1 WO 1990003145A1 US 8903613 W US8903613 W US 8903613W WO 9003145 A1 WO9003145 A1 WO 9003145A1
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Prior art keywords
compliance
distal
patient
disease condition
vascular
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PCT/US1989/003613
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English (en)
Inventor
Jay N. Cohn
Stanley M. Finkelstein
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Regents Of The University Of Minnesota
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Publication of WO1990003145A1 publication Critical patent/WO1990003145A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
    • A61B5/021—Measuring pressure in heart or blood vessels

Definitions

  • the present invention relates generally to the fields of cardiac and circulatory medicine, and more particularly to the medical disorder of hypertension.
  • Hypertension is traditionally defined as abnormally elevated blood pressure. More specifically, when a person under conditions of rest consistently has a blood pressure that exceeds 145/90 (systole/diastole) , the person is said to have high blood pressure or hypertension. It is currently believed that over fifty million people in the United States have hypertension and fifteen to twenty percent of all deaths in people over fifty years of age occur as a direct or indirect result of hypertension. Actuarial statistics show that the disability and mortality rates of hypertensive persons are higher for each age bracket than for persons with normal blood pressure. Specific ailments attributable to hypertension include heart failure, myocardial infarction, rupture or thrombus of the blood vessels in the brain and kidney damage.
  • This deficiency manifests itself in various ways. For one, it can result in unnecessary and undesirable antihypertensive treatment for individuals who are diagnosed as borderline hypertensive due to an elevated blood pressure above the statistical norm of 145/90 but who are actually healthy and do not have the hypertensive disease condition. Administering antihypertensive therapy to such healthy patients would subject them to its potentially undesirable side effects. This is clearly ill advised.
  • certain individuals may exhibit normal blood pressure as it is statistically defined, yet suffer from the underlying hypertensive disease condition. These individuals may benefit from antihypertensive therapy yet it would not, according to current practices, be prescribed for them.
  • the modified Windkessel model investigated by Watt and Burrus is a third-order electrical model of the arterial system.
  • the model includes two capacitive elements, C x and C 2 , an inductance component L and a resistance component R.
  • C x corresponds to the "proximal vascular compliance", defined as the collective elastic compliance of major arteries nearest the heart, C 2 to that of “distal vascular compliance”, defined as the vascular compliance of smaller peripheral arteries and arterioles further from the heart, L to the collective inertia of major blood columns, and R to the total vascular resistance assumed to be located primarily in arterioles and capillaries.
  • the present invention finally provides such a tool.
  • the present invention provides method and apparatus for the detection, diagnosis, monitoring and treatment of hypertension. More specifically, the present invention calls for measuring the distal compliance of a patient's vascular system and for using the measured compliance as a marker or indicator of the hypertensive disease condition.
  • the parameter C 2 of the modified Windkessel model is used as a measure of distal vascular compliance.
  • apparatus for monitoring blood pressure waves and determining the value of the parameter C 2 is provided.
  • Figure 1 is a skematic drawing of the modified Windkessel model of the human vasculature
  • Figure 2 is a plot of mean arterial pressure (MAP) versus C 2 for a group of normotensive subjects and a group of hypertensive patients as diagnosed by blood pressure cuff (sphygmo anometer) measurements;
  • Figure 3 is a schematic block diagram of the monitor according to the present invention.
  • Figure 4a and 4b comprise a schematic flow chart of the software of the present invention
  • Figure 5 is illustrative example of typical arterial pulse contours in healthy patients
  • Figure 6 is illustrative example of typical arterial pulse contours in diseased patients
  • Figure 7 is a schematic view diagram of the software to be used in the clinic computer according to the present invention.
  • Figure 8 is a plot of C 2 versus MAP for hyper- and normo-tensive patients.
  • Figure 9 is a plot of C versus MAP for hyper- and normo-tensive patients.
  • the present invention is based on the results of a study of the vasculature of a group of hypertensive patients and a group of normotensive patients.
  • the hypertensive patiefats all had a confirmed history of elevated blood pressure with blood pressure cuff measurements exceeding 145/90 at the time of the study.
  • the normotensive subjects all had blood pressure cuff measurements below 145/90.
  • the modified Windkessel model of the arterial system is shown in Fig. 1. In the model,
  • P23Db pressure transducer This catheter-transducer system has an undamped natural frequency higher than 25
  • Blood pressure waveforms were recorded for 30 seconds for each subject in a supine position, after at least 60 minutes of supine rest after catheter positioning. All hemodynamic data were recorded on both paper and magnetic tape. Data were digitized using a 12- bit analog to digital converter operating at 200 samples per second per channel. Digitized data were saved on disk for subsequent beat marking, signal processing and pulse-contour analysis. The onset and end of diastole for the brachial artery pressure waveform were marked on six consecutive beats and the modified Gauss-Newton parameter-estimating algorithm was run on each marked beat. Each group of six consecutive beats was selected manually from each 30-second record by choosing the group with the most noise-free pressure and phonocardiogram signals as viewed by the operator. The diastolic waveform for each beat can be represented most generally as the third-order function:
  • Fig. 2 shows the plotting of the mean arterial pressure (MAP) versus distal compliance as quantified by the measured C 2 parameter for all of the subjects in the study, with the normotensive patients represented by circles and the hypertensive patients represented by squares.
  • mean arterial pressure is approximately equal to the diastolic pressure measurement plus one-third the difference between the systolic and diastolic measurements.
  • a 145/90 cuff measurement would equate to a mean arterial pressure of about 108 mm Hg.
  • C 2 varies widely in normotensive subjects but is consistently reduced in subjects with hypertension.
  • the plot also shows a generally linear decrease in the measured C 2 compliance value with increase in mean arterial pressure.
  • the results of this study thus establish: 1) hypertensive subjects have consistently reduced distal vascular compliance; 2) distal vascular compliance is independent of blood pressure, i.e. two persons with the same blood pressure can have widely varying distal compliance, particularly among normotensive subjects; 3) there is a distinct division between distal vascular compliance measurements for normotensive and hypertensive patients; and 4) the underlying physical condition of distal vascular compliance, as quantified by C 2 measurements, can be used as a marker for or an indicator of the hypertensive disease condition.
  • the study also supports the following inferences: 1) a normotensive or borderline hypertensive patient with a normal C 2 value is unlikely to develop the hypertensive disease condition and its associated chronic hypertension; and 2) normotensive or borderline hypertensive subjects with reduced C 2 values are more likely to develop chronic hypertension than normotensive or borderline hypertensive subjects with normal C 2 values.
  • the results of the study described and discussed above thus establish that distal vascular compliance is a specific marker for the hypertensive disease condition and that diagnosis and drug therapy of the disease called hypertension can be made more precise by measurement of C 2 than by measurement of cuff blood pressure alone.
  • the blood pressure may vary widely and may be normal on many occasions in some patients who have the hypertensive disease condition and may be high on occasions in patients who do not have the hypertensive disease condition.
  • the measurement of blood pressure alone is not useful in identifying patients who have the hypertensive disease condition.
  • the C 2 measurement will be reduced in patients who have the hypertensive disease condition regardless of blood pressure and will be normal in patients who do not have the hypertensive disease condition regardless of their blood pressure. Therefore, distal vascular compliance (i.e. C 2 measurements) can serve the unique purpose of identifying the hypertensive disease condition, particularly in patients with borderline blood pressures which may sometimes be normal and sometimes be elevated.
  • distal vascular compliance as a marker for the hypertensive disease condition has several important clinical applications, some of which are specified as follows.
  • distal vascular compliance measurements can be used to exclude from unnecessary antihypertensive therapy, patients whose blood pressure may periodically be elevated but who do not actually have the hypertensive disease condition.
  • the present invention provides a method for determining treatment for a patient with borderline hypertension comprising: 1) determining for the patient a measure of distal vascular compliance; and 2). administering medications known to raise distal vascular compliance (i.e. make the vessels less stiff and more elastic) if said distal compliance is less than the threshold band defined below.
  • the patient can be identified as one not likely to benefit from administration of medication which increases distal compliance if the patient's distal compliance is greater than the threshold band defined below.
  • a patient is defined as borderline hypertensive if his blood pressure is sometimes elevated and in the hypertensive range but is at other times is normotensive.
  • Another application of the present invention is the use of distal vascular compliance measurements for identifying the hypertensive disease condition and/or quantifying its severity.
  • This method comprises the steps of: 1) determining for the patient a measure of distal vascular compliance; 2) diagnosing the patient as having the hypertensive disease condition if his distal vascular compliance is within or less than a predetermined diagnostic threshold band; and 3) diagnosing the patient as not having the hypertensive disease condition if his distal compliance is greater than the threshold band.
  • the threshold band is the summed region of individual vascular compliance values taken from a statistically significant number of patients who have been diagnosed as having mild to severe ,hypertension.
  • an average threshold value can be obtained by averaging the hypertensive patient compliance values that establish the foregoing threshold band.
  • This threshold value can be substituted for the threshold band in the foregoing method.
  • Patients with a distal vascular compliance less than or about equal to this average threshold value are diagnosed as having the hypertensive disease condition (such patients may have normal or elevated blood pressure) .
  • Patients with a distal vascular compliance greater than the average threshold value are diagnosed as being essentially free of the hypertensive disease condition.
  • a conservative approach can also be employed whereby only those patients having a distal compliance greater than the average threshold value plus its standard deviation are diagnosed being essentially free of the hypertensive disease condition.
  • persons determined to be hypertensive by blood pressure cuff measurements can be further tested to determine their distal vascular compliance. If their distal vascular compliance is above a certain level, the person can be diagnosed as not likely to benefit from antihypertensive drug therapy designed to raise distal vascular compliance and, moreover, as perhaps only suffering from a transient elevation of blood pressure.
  • the distal vascular compliance measures can be used to assess the severity and/or the likelihood that a particular individual with hypertension will respond to treatment. For instance, persons with only marginally high blood pressure but having very poor distal compliance, e.g. C 2 measurements of about 0.02 ml/mm Hg, can be classified as having a severe hypertensive disease condition (although they are only mildly hypertensive) .
  • a method for early detection of the development of the hypertensive disease condition comprising the steps of: 1) measuring the distal vascular compliance of the patient; 2) repeating step 1) over a period of time and charting the course of distal vascular compliance; and 3) diagnosing a movement toward the onset of the hypertensive disease condition if the course of charted distal compliance is trending downwardly indicating stiffening or hardening of distal arteries.
  • Another application of the discovery of the present invention comprises a method for monitoring the progress of the hypertensive disease condition comprising the steps of:
  • distal compliance as a marker of or indicator for the hypertensive disease condition. These applications provide methods for detecting, diagnosing, monitoring and treating the hypertensive disease condition.
  • the present invention contemplates using the C 2 parameter of the modified Windkessel model as a measure of distal vascular compliance. It shall be understood, however, that other measures of distal compliance, if developed, would also work in applying the various methods and principles of the present invention contemplated herein.
  • distal vascular compliance is in essence defined as the physiologic attribute measured by the C 2 and is influenced by other processes in the vascular system including cardiovascular aging; atherosclerosis; medial arteriosclerosis; vascular infiltrative processes; vascular inflammatory processes; vascular hypertrophy and other deleterious vascular conditions which are not presently ellucidated, and which would produce a reduction of C 2 values. Accordingly, it shall be understood that the use of other measurement methods for determining vascular compliance and identifying underlying disease states such as those mentioned in the foregoing discussion, are within the scope of the methods and principles of the present invention.
  • a distal vascular compliance within or below a C 2 threshold band of from about 0.05 to 0.08 indicates, with a reasonably high degree of certainty, that the patient has a vascular abnormality or abnormalities associated with hypertension, aging, atherosclerosis or other vascular disease.
  • a distal vascular compliance at or below a C 2 threshold value of about 0.05 ml/mm Hg indicates, with a high degree of certainty, that the patient is suffering from the hypertensive disease condition and/or another vascular abnormality(ies) .
  • the particular C 2 value selected as the threshold value for individual clinical application is to some degree a matter of choice. For instance, it may be desirable to diagnose borderline hypertensive patients (i.e. those diagnosed through repeated blood pressure measurements) with C 2 measurements below a threshold value of about 0.12 ml/mm Hg as likely to benefit from antihypertensive therapy directed toward raiding distal vascular compliance. In such cases antihypertensive therapy might reduce the patient's prevailing blood pressure level so that transient increases in blood pressure, as for example caused by stress, would not exceed dangerous levels whereby a blood vessel might rupture and result in a stroke.
  • the average threshold value method when employing the average threshold value method, it may be desirable to choose a second, different average threshold value above which the patient is diagnosed as being essentially free from a hypertensive disease condition.
  • the results presented herein indicate that a patient with a distal vascular compliance at or above an average threshold C 2 value of about 0.08 ml/mm Hg would, with a high degree of certainty, be essentially free of the hypertensive disease condition.
  • Patients with C 2 values between those of the average hypertensive and normotensive threshold values, i.e. those within the threshold range, could be diagnosed as borderline cases if other clinical conditions are confirmatory.
  • the present invention also provides apparatus for measuring, monitoring and diagnosing the hypertensive disease condition.
  • the vascular compliance apparatus 10 according to the present invention is shown in schematic block diagram form in Fig. 3.
  • the monitor 10 includes an analog to digital convertor (A/D) 12, preferably 12-bit, a microprocessor unit 14, for instance a 6502 model by
  • Transducer 34 is preferably a Statham P23Db pressure transducer, and it is preferably connected to a brachial artery by an 18-gauge, 2-inch Teflon catheter. This catheter-transducer system has an undamped natural frequency higher than 25 HZ and a damping coefficient less than 0.5, providing an acceptable frequency response. It shall be understood, however, that while the brachial artery is preferred, other arterial peripheral locations for obtaining the pulse pressure contour could readily be substituted. Moreover, it is contemplated that a non-invasive method for measuring arterial pressure waves could also be used.
  • the software component 50 of the monitor 10 is illustrated in block diagram flow-chart form in Figs. 4a and b.
  • Software within 10 is preferably maintained in ROM 20 and is referenced by microprocessor 14.
  • software 50 could be stored in magnetic form on a floppy computer disk connected so as to be accessed by monitor 10.
  • software 50 runs on microprocessor 14 to control the acquisition of artery pressure pulse data, and to process, analyze and diagnose the acquired data.
  • An initialization and mode select routine 52 is provided for initializing microprocessor 14, including prompting the user to enter the date (and certain desired patient information) . Routine 52 further allows either the monitor mode or communication mode to be selected. If the monitor mode is selected, A/D convertor 12 is activated (54) to digitize the analog brachial pressure pulse signal generated by transducer 34 in its position in the patient's brachial artery. Referring to Figs. 5 and 6, there are illustrated typical brachial artery pulse pressure contours for healthy, normotensive and hypertensive patients, respectively. The present invention uses an A/D sampling rate of 200 samples/second, which is satisfactory to capture the highest frequency components of interest in the brachial pressure pulse.
  • Routine 56 provides that the artery is monitored for approximately 30 seconds, producing in the range of 25 to 60 digitized pulses, depending on the heart rate.
  • the stream of digitized pulses are stored in RAM 22 in the form of a continuous series of periodic time dependent data byte samples, with each data byte corresponding to the instantaneous pressure of the artery.
  • Routine 60 is provided for acquiring a cardiac output value, which is required for calculation of impedance parameters as explained in more detail below.
  • cardiac output is input directly from keyboard 16 in liters/minute (or alternatively, milliliter/second) .
  • Cardiac output may be determined by the thoracic impedance technique using for example the Minnesota Impedance Cardiograph model 30413, with the results being manually transferred to apparatus 10.
  • another non-invasive instrument may be used for this purpose, with the measured output being transmitted directly into monitor 10 through a microprocessor port.
  • a selection routine 20 is also provided to analyze the recorded waves and to select a group of at least six consecutive representative beats preferably of comparatively low noise content.
  • Representative beats are identified by establishing windows of permissible heart rate and mean arterial pressure values whereby abnormally fast or slow heartbeats, or high or low pressures can be rejected.
  • the routine can thus pick the series of beats which is most representative. Where possible it is preferable that the windows be tailored to the patient, thus allowing more precise selection of representative beats.
  • a routine 72 is provided to identify the relevant portions.
  • a clinician can identify the onset of diastole by correlating to the second heart sound S 2 , and the end of diastole by the upstroke of the following pulse. For example, in Figs. 5 and 6 diastole is marked by the respective segments A and B.
  • the present invention uses a software analysis algorithm to predict and select the segment in each wave most probably corresponding to diastole.
  • routine 72 searches for the dicrotic notch (D) , and marks the onset of diastole just before the location of the dicrotic notch on the wave. The end of diastole in the waveform is easily located by finding the upstroke of the next pulse.
  • device 10 could include means for digitizing an analog signal representing the heart sounds, and software for identifying the second heart sound S 2 and correlating it to the digitized arterial waveform to identify the onset of diastole. This process could also preferrably be accomplished by a computer software program. With the relevant segments marked the data for each pulse can be analyzed to reveal the vascular compliance properties of the patient.
  • the modified Windkessel model of the arterial system is used in the pulse contour analysis of the present invention.
  • the model includes components P ⁇ r P 2 , C l r C 2 , L and R in which:
  • C x proximal vascular compliance (ml/mm Hg)
  • C 2 distal vascular compliance (ml/mm Hg)
  • L inertance (mm Hg/ml/s 2 )
  • R peripheral resistance (dynes x seconds x cm "5 ) As taught for example by Goldwyn and Watt in
  • routine 80-82 comprises a modified Gauss-Newton parameter-estimating algorithm as for example referenced by Watt and Burrus in their paper entitled “Arterial Pressure Contour Analysis for Estimating Human Vascular Properties", Journal of Applied Physiology, 1976; 40:171- 176, the disclosure of which is hereby incorporated herein by reference.
  • Routine 80-82 calculates the optimal values for coefficients A ⁇ Ag, using the measured brachial arterial pressure as P 2 (t) .
  • the algorithm uses an iterative approach which preferably provides fast convergence.
  • the algorithm used in routine 80-82 includes certain modifications.
  • An automatic stopping procedure is included to stop iteration when an acceptable error level in the curve fitting threshold is reached or when convergence provides no further substantial fit of the curve. Also, when the process begins to diverge, it returns to the previous best case.
  • the routine also includes a weighted iteration interval to improve convergence.
  • the coefficients are used at routine 84 to calculate the C lf C 2 and L vascular impedance parameters for each pulse contour.
  • C lf C 2 and L are all calculated in accordance with the formulas given above.
  • the calculated values are average at routine 86, producing mean values more reliable for accuracy than any individual values. It shall be understood, however, that the averaging process is not essential. For instance, a median value could be selected for use if desired.
  • the distal compliance parameter C 2 is stored in RAM 22. Monitor 10 is further operative to analyze the acquired distal vascular compliance values in order to indicate the likelihood of unlikelihood of the hypertensive disease condition in the patient being monitored.
  • diagnostic analyses are performed at the end of each monitoring operation. It is contemplated, however, that diagnosis could be initiated under independent keyboard 16 control if desired.
  • the first diagnostic test performed is preferably a threshold test, performed at routine 100 to determine whether the distal compliance (C 2 ) value is above, below_or in betwe one or more threshold values which are preferably predetermined and stored in RAM 22 and RAM 20.
  • Routine 100 can be programmed in accordance with the diagnostic methods outlined hereinabove.
  • routines 102 and 110 are also provided for diagnostic purposes, and provide for analyzing dista vascular compliance values accumulated over time to determine the slope or trend of the values over time, fo instance over a month or a year.
  • routines 102 and 110 can anticipate a trend toward the hypertensive disease condition as indicated by diminishing distal vascular compliance values and evaluate the significance or abruptness of the trend.
  • a trend toward improved distal compliance can also be determined, indicating an improvement of the hypertensive disease condition, as may result from beneficial therapy.
  • Routine 110 also optionally includes diagnostic logic to evaluate the interrelationship between C 2 values and the slope of the values, or other desirable criteria, to provide more sophisticated diagnosis.
  • Routine 120 is provided to indicate via display 18 the value of the C 2 parameter determined by the software and the result of the threshold tests provided at routin 100, whereby, for instance, when distal compliance falls below the selected threshold value, a likelihood of the hypertension disease condition is indicated.
  • Routine 14 is also provided to report (140) the analysis results on an optional printer 42.
  • a warning routine 130 is provided to cause monitor 10 to produce a warning indication, eithe through display 18, or in a printed report (140) the analysis results on an optional printer 42. .
  • Monitor 10 also includes communications capability, whereby accumulated C 2 data (or, if desired other stored vascular parameters) may be communicated to further computer equipment 44 in a clinic or hospital, such as a personal computer or minicomputer. Accordingly, monitor 10 may be used by a patient at home with measured and stored parameters particularly C 2 , being transmitted back to a treating hospital or clinic for review or for further analysis.
  • software 50 provides a communications mode including routines 145 and 146, which provide for establishing a communication link with remote system and for downloading selected information including accumulated C 2 values.
  • a clinic or hospital computer 44 is provided to communicate with monitor 10 using a standard mode -telephone link.
  • Figure 7 illustrates in diagrammatic form the software 150 provided for clinic computer 44.
  • a routine 152 is provided for establishing the communication link with monitor 10.
  • Computer 44 preferably includes an auto-answer modem so that monitor 10 may establish unication therewith with a minimum of effort.
  • Data acquisition routine 154 is provided to receive C 2 values and other desired data which may be stored in RAM 22, such as cardiac output, mean arterial pressure, C 1; L and slope data.
  • Routine 156 is provided to evaluate C 2 and, optionally, other vascular properties. Routine 156 includes all the capabilities described with respect to monitor 10 (routines 100, 102, 110), and preferably more sophisticated analysis techniques which would take into account other known patient data, such as the patient's medical history. At a minimum, routine 156 provides for a printed report of acquired C 2 values which may be reviewed by the treating personnel or physician. Finally, a routine 158 is provided to suggest therapy strategy based on the results of evaluation 156.
  • the study described in the foregoing section was extended to include a larger group of hypertensive (hyp) and normotensive (N) Patients.
  • the MAP mean arterial blood pressure
  • C x and C 2 were determined for these patients as described above.
  • the protocol employed was as follows.
  • Each patient was catheterized with an 18 gauge transcutaneous Teflon catheter inserted into his brachial artery. Pressures were obtained from a Statham P23b pressure transducer connected to the catheter. The procedures for inserting the catheter, measuring and recording waveform cardiac output and computing values for C x and C 2 were applied as described in the foregoing section.
  • the results of the MAP, C x and C 2 measurements and the hyper-(hyp) or normo-(N) tensive nature of each patient are summarized in Table 1.
  • the average C 2 hyp measurement is 0.018 with a deviation of 0.025.
  • the average C 2 N measurement is 0.115 with a deviation of 0.06.
  • the C 2 results from this study are plotted against MAP in Figure 8.
  • the "0" points are hypertensive.
  • the "X” points are normotensive.
  • the plot shows that C 2 values of hypertensives consistently fall at or below 0.05 ml/mmHg and define a readily discernable threshold band in the hypertensive MAP region. This band recognizably falls below the normotensive C 2 region.
  • the C- L results from this study are plotted against

Abstract

Le procédé décrit qui sert au diagnostic, au traitement et au contrôle de l'hypertension, utilise le paramètre C2 (c'est-à-dire l'élasticité vasculaire distale) du modèle de Windkessel modifié comme indication de l'état de maladie hypertensive. Un appareil permettant de déterminer le paramètre C2 du modèle de Windkessel modifié comprend un organe permettant d'obtenir une courbe d'impulsions de pression et une valeur de sortie cardiaque et permettant de déterminer les paramètres du modèle.
PCT/US1989/003613 1988-09-28 1989-08-22 Procede et appareil de diagnostic et de traitement de l'hypertension WO1990003145A1 (fr)

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US25031588A 1988-09-28 1988-09-28
US34192389A 1989-04-24 1989-04-24
US250,315 1989-04-24
US341,923 1989-04-24

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EP0564492A1 (fr) * 1990-12-28 1993-10-13 Regents Of The University Of Minnesota Instrument de mesure d'impedance vasculaire
US6758822B2 (en) 1999-04-27 2004-07-06 Salvatore Romano Method and apparatus for measuring cardiac output
US7220230B2 (en) 2003-12-05 2007-05-22 Edwards Lifesciences Corporation Pressure-based system and method for determining cardiac stroke volume
US7422562B2 (en) 2003-12-05 2008-09-09 Edwards Lifesciences Real-time measurement of ventricular stroke volume variations by continuous arterial pulse contour analysis
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JP3721743B2 (ja) * 1997-10-03 2005-11-30 セイコーエプソン株式会社 心機能診断装置
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Publication number Priority date Publication date Assignee Title
EP0564492A1 (fr) * 1990-12-28 1993-10-13 Regents Of The University Of Minnesota Instrument de mesure d'impedance vasculaire
EP0564492A4 (fr) * 1990-12-28 1994-10-12 Univ Minnesota Instrument de mesure d'impedance vasculaire.
US5876347A (en) * 1990-12-28 1999-03-02 Regents Of The University Of Minnesota Method for vascular impedance measurement
US6758822B2 (en) 1999-04-27 2004-07-06 Salvatore Romano Method and apparatus for measuring cardiac output
US7220230B2 (en) 2003-12-05 2007-05-22 Edwards Lifesciences Corporation Pressure-based system and method for determining cardiac stroke volume
US7422562B2 (en) 2003-12-05 2008-09-09 Edwards Lifesciences Real-time measurement of ventricular stroke volume variations by continuous arterial pulse contour analysis
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IL91794A0 (en) 1990-06-10
AU4197989A (en) 1990-04-18
JP3122105B2 (ja) 2001-01-09

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