WO2005067387A2

WO2005067387A2 - Apparatus and method for calculating velocity of blood pressure change

Info

Publication number: WO2005067387A2
Application number: PCT/IL2005/000054
Authority: WO
Inventors: Miguel Gorenberg; Hector Rotstein; Alon Marmor; Michael Naroditzky
Original assignee: Cardiowatch Ltd.
Priority date: 2004-01-16
Filing date: 2005-01-16
Publication date: 2005-07-28
Also published as: WO2005067387A3

Abstract

A non-invasive apparatus for measuring the variations of the blood pressure of a patient with respect to time, the apparatus comprising a pressure applying element mountable on a limb of the patient for applying pressure high enough to make a segment of an artery within the limb achieve a collapsed state and empty it from blood at least momentarily; a multi-sensors coupled to the pressure applying element, sensing mechanical changes corresponding to volumetric changes in the artery as the artery progressively recuperates from its collapsed state; processing unit communicating with the sensors for receiving output corresponding to the mechanical changes from the sensors and computing factors correlated with blood flow and calculate parameters indicating heart performance. A say multisensor with sensing material made from piezo-resistive material.

Description

APPARATUS AND METHOD FOR CALCULATING VELOCITY OF BLOOD PRESSURE CHANGE

BACKGROUND OF THE INVENTION - FIELD OF THE INVENTION

This invention generally relates to the monitoring of the mechanical performance of the heart, specifically to an apparatus and method for measuring the velocity of change of the blood pressure in the aorta.

BACKGROUND OF THE INVENTION - DISCUSSION OF PRIOR ART

Ischemia Heart muscle ischemia due to coronary artery diseases is one of the leading causes of death in the world; in the United States alone, it affects more than 13 million people. Myocardial ischemia can be defined as a decrease in the supply of blood to the heart, and more precisely as an imbalance between the supply and demand of myocardial oxygen. In most clinical situations, the reason for this imbalance is inadequate perfusion of the myocardium due to obstructions or stenosis of the coronary arteries. The ischemia can last a few seconds or persist for minutes or even hours, causing transient or permanent damage to the heart muscle. Each year, an estimated amount of 1 million Americans will have a new or recurrent coronary attack while more than 40% of the people experiencing coronary attack are expected to die resulting from it. Ischemia can be treated in health-care facilities once it is detected. In the early stages, a person suffering from ischemia may not experience a clear external manifestation, e.g., chest pain, and his or her condition may aggravate, possibly in an irreversible manner. Hence the importance of having an efficient and reliable monitor for ischemic condition. Cardiologists attempt to use an Electro-Cardiogram (ECG) to monitor ischemic incidents in patients. An ECG measures the electrical activity of the heart. However, it may take some time for ischemia to affect the electrical activity and indeed ECG tests have been shown in studies to have low sensitivity for diagnosis of ischemia (about 60%).

Monitoring the Mechanical Performance of the Heart

Experimental and clinical studies in the cardiologic literature and other references indicate that changes in the cardiac mechanical performance occur relatively early when an incidence of ischemia takes place, and indexes reflecting the mechanical performance of the heart are more sensitive than ECG changes or subjective symptoms for detecting myocardial ischemia. See: Kayden et al., "Validation of Continuous Radionucleide Left Ventricular Functioning Monitoring in Detecting Silent Myocardial Ischemia during Balloon Angioplasty of the Left Anterior Descending Coronary Artery", Am. J. Cardiol. 67, 1339-1343 (1991), In this work the authors used balloon inflation in the course of a medical intervention as a human model of transient myocardial ischemia due to acute reduction of coronary blood flow. They show that out of 18 patients, 17 inflations were followed with a significant decrease in Left Ventricular Ejection Fraction. In contrast, there was chest pain in only 10 inflations and ECG changes in 7. In a work by T. Sharir et. al. in cooperation with one of the inventors of the monitor disclosed in this patent, it was shown that the rate of pressure rise during the cardiac ejection phase increases with physical effort and decreases with infusion of vasodilating drugs. See: Sharir T, Marmor A, Ting CT, Chen JW, Liu CP, Chang MS, Yin FCP and Kass DA. Validation of a method for noninvasive measurement of central arterial pressure. Hypertension 1993, 21 74-82. The device used in that work is based in part on measurements of peripheral flow parameters and is described also in US patent 5,199,438. The apparatus used by these inventors consists of an ECG, a Doppler sensor and an inflatable cuff and is hence too cumbersome to be used outside a specialized medical facility. It follows from these and other works reported in the medical literature that sensors based in monitoring the mechanical performance of the heart are superior to methods monitoring the electrical performance or those base on physical evidence. Monitors for the Mechanical Performance of the Heart

Cardiac performance can be monitored by measuring the peripheral blood flow. The peripheral flow can be monitored by using electromagnetic sensors as disclosed in US patent no. 4,412,545 by Okino et al. "Electromagnetic Blood Flowmeter" and in PCT/IL01/00583 (Gorenberg et al.), titled APPARATUS AND METHOD FOR NON-INVASIVE MONITORING OF HEART PERFORMANCE, published as WO/02/00094. However, the peripheral blood flow on its own is not a proven indicator of cardiac performance. Hence it is desired to measure peripheral hemodynamics parameters more indicative of the cardiac performance. A family of sensors for non-invasive measurements of hemodynamics parameters have also been proposed by Tomita and co-workers in the patents US 5,095,912, US 5,301,675, US 5,316,005, US 5,388,585, US 5,406,954, US 5,423,324, US 5,651,369 and US 6,231,523. These patents disclose devices for detecting pressure waves coupled with a plurality of bags and an occluding cuff over the upper arm. By monitoring the appearance of Korotkoff sounds or the pressure wave and using empiric formulas, different parameters of the hemodynamics system can be estimated. The fact that the methods proposed by these inventors are based on the Korotkoff sounds makes them unreliable and susceptible to changes unrelated to the hemodynamics index they attempt to measure. Moreover, the usage of a measuring bag makes their measure non-localized, hence further adding to the intrinsic errors in the measurement. US 6,319,205 (Goor) and US 6,322,515 (Goor) disclose yet another apparatus and method for monitoring physiological changes by performing a continuous monitoring of the arterial tone at the digit of the subject. Some of the embodiments in Goor involve mounting a cuff around the digit, application of pressure and monitoring the tone at the extreme end of the digit. All these methods are based on measuring the tone of an artery in the periphery and using an empiric model to estimate measurements of cardiac performance. The model is an approximation to the behavior of the hemodynamics systems of patients, and hence changes from patient to patient, and also for the same patient at different times. Consequently, the method is susceptible to errors when not calibrated to a specific patient. Furthermore, Millar disclosed in US 5,503,156 a noninvasive pulse transducer for simultaneously measuring pulse pressure and velocity. The sensor disclosed in Millar's invention may have application in hemodynamics measurements but requires the usage of a Doppler sensor. Doppler sensors are susceptible to several error sources and needs to be used by a professional healthcare provider with experience in Doppler measurements. Cardiac performance can also be estimated by monitoring the blood pressure on the left ventricle of the heart. Here and in what follows it is understood that blood pressure is a continuous, pulse-like function giving the pressure of the blood fluid inside an artery as a function of time. It should not be confused with the systolic and diastolic blood pressures, which are the two special values of this function that are provided by existing blood pressure measurement devices. Blood pressure is hard to measure in a non-invasive manner, but numerous methods exist for measuring the systolic and diastolic pressures (S&DP). A method for measuring S&DP is the oscillometric method. Oscillometric blood pressure measurements are made by using a transducer to detect and measure pressure waves in a pressure cuff as blood surges through an artery constricted by the pressure cuff. Many currently available digital blood pressure monitors use the oscillometric method for determining blood pressure. Although S&DP pressure is relatively easy to measure, it has been shown to be an unreliable monitor of heart performance in general and of ischemia in particular.

There has been significant research directed toward the development of new non-invasive techniques for monitoring blood pressure. One approach exploits the correlation between blood pressure and the time taken for a pulse to propagate from a subject's heart to a selected point on a subject's artery. This approach is possible because the speed at which pulse waves travel from the heart to points downstream in a subject's blood circulatory system varies with blood pressure. As blood pressure rises the propagation velocity of arterial pulse wave increases and the pulse transit time decreases. In general, such methods may be called Pulse Transit Time (or "PTT") methods. Typically a signal from an ECG is used to detect a heart beat and a pressure sensor is used to detect the arrival of a pulse wave generated by the heart beat at a downstream location. This approach is described, for example, by Inukai et al., U.S. Pat. No. 5,921,936. The Inukai et al. system uses an electrocardiogram to detect the start of a heart beat and uses a cuff equipped with a pressure sensor to detect pulse waves. Other similar systems are described in Orr at al., European Patent application No. EP0181067. A variation of this approach is described in Golub, U.S. Pat. No. 5,857,975.

Chen et al. disclosed in U.S. Pat. No. 6,599,251 still one more method for computing blood pressure. In the patent, Chen et al. reviewed methods for computing blood pressure which are relevant to the invention disclosed here since they reviewed methods based on the PTT. One difficulty with PTT blood pressure measurement systems which measure blood pressure as a function of the time between the pulse of an ECG signal and a detected pulse wave is that there is a delay between the onset of an ECG pulse and the time that the heart actually begins to pump blood. This delay can vary significantly in a random way, even in healthy subjects. Hatschek, U.S. Pat. No. 5,309,916 discloses a method for measuring blood pressure by determining the time taken for a pulse to propagate downstream along a single arterial branch. This approach eliminates uncertainties caused by the imperfect correlation between ECG signals and the delivery of blood by the heart. However, it has the disadvantage that it can be difficult to arrange two sensors so that they can detect a pulse at each of two widely spaced apart locations along a single arterial branch.

The book entitled Monitoring in Anesthesia and Critical Care Medicine, 3rd Edition, edited by Blitt and Hines, Churchill Livingstone, 1995, mentions a blood pressure monitor having the trade name, ARTRAC TM 7000 using two photometric sensors, one on the ear and another on a finger, to measure diastolic blood pressure. This device apparently used the difference in arrived times of pulses at the ear and finger to measure the pulse transit time. The diastolic pressure was estimated based on a relationship of pressure and pulse wave velocity. This device apparently computed systolic pressure from the pulse volume. Further information about this device is provided in a FDA 510(k) Notification entitled, "ARTRAC.TM. Vital Sign Monitor, Models 7000 and 5000 (K904888)," submitted by Sentinel Monitoring, Inc., 1990.

A relationship between blood pressure and pulse transit time can be developed by assuming that an artery behaves as if it were a thin-walled elastic tube. This relationship, which is known as the Moens-Korteweg-Hughes equation is described in detail in the article Terminology for Describing the Elastic Behavior of Arteries by G. Gosling and M. Budge, published in the journal Hypertension. 2003;41:1180. The Moens-Korteweg-Hughes equation depends on the elasticity and geometry of blood vessels and is highly nonlinear.

Inventors Aso et al., U.S. Pat. No. 5,564 427, proposed the, use of a linear equation to calculate blood pressure using the ECG based pulse transit time. This method was further developed by Hosaka et al., U.S. Pat. No. 5,649,543. To calibrate the linear measurement system, Sugo et al., U.S. Pat. No. 5,709,212, introduced a multi-parameter approach to determine the parameters at deferent blood pressure levels for systolic and diastolic pressures respectively. Shirasaki patented another method to calibrate the parameters based on the multiple blood pressure reference inputs in Japanese patent No. 10-151118. All these inventions based on the PTT suffered from the following common difficulties: 1) They need to synchronize an ECG pulse with a signal at a different part of the body hence requiring calibration of an heuristic formula, and 2) The PTT is usually very short, since the velocity of the pressure wave is large, hence requiring a precise, error prone, measurement. Our previous patent US.10,234,429 describes a method and apparatus for monitoring the cardiac performance by estimating the cardiac performance index (CPI). Although this index has been shown by the authors to provide a good indication of heart performance under stress conditions, it is not well established in as an indicator of heart performance in the medical community. The velocity of chance of the blood pressure with respect to time, called DP/DT in the art, has been recognized as a useful parameter for monitoring the cardiac performance. Existing methods for measuring DP/DT are either invasive, hence requiring a special medical intervention, or non-invasive but requiring expensive and cumbersome equipment. BACKGROUND OF INVENTION - OBJECTS AND ADVANTAGES

Accordingly, besides the objects and advantages discussed in the previous patent by the same inventors US10,234,429, several objects and advantages of the present inventions are: (a) To provide a new and unique noninvasive device and method for monitoring, periodically or continuously, the mechanical performance of the heart. (b) To provide a new device and method for measuring the velocity of change of a blood pressure pulse, called DP/DT (the derivative of the pressure with respect to time) in the art. (c) To provide a new device and method that is similar in operation to a blood pressure monitor and hence can be used by practitioners with minimum training. (d) To provide a new device and method for monitoring the mechanical performance of the heart that provides reliable results under uncontrolled measurement conditions. (e) To provide a new device and method for monitoring the mechanical performance of the heart that requires no calibration for a given patient. (f) To provide a new device and method for monitoring the mechanical performance of the heart based on direct mechanical principles. (g) To provide a new and unique device and method for monitoring the mechanical performance of the heart while the device is preferably mounted on the upper arm, the lower arm or the wrist, so that comfortable measurements conditions are met. The device may be mounted on another peripheral organ or area that meets the requirements of which blood flow may be measured without interference. (h) To provide a new device that alerts patents to seek for immediate medical assistance when their heart performance is deteriorating.

(i) To provide a new device that facilitates true diagnosis in cases of ischemia so that false positive and false negatives ECG interpretation is avoided.

0) To provide a new device and method for recording and storing synchronized ECG signals with parameters that are correlated to the mechanical cardiac performance for relatively long periods of time (24 - 48 hours or even more) so as to provide an improved Holter system.

(k) To provide a new device to facilitate the diagnosis of obstructive sleep apnea syndrome by monitoring changes in peripheral vascular resistance (PVR).

(I) To provide a new device to facilitate the diagnosis of endothelial dysfunction, by monitoring changes in the flow of blood under mechanical or chemical extrinsic changes.

(m) To provide a new device and method to facilitate ruling out potential cardiac dysfunction, by comparing the parameter described herein below against a pre-fixed threshold. (n) To provide a new device and method for augmenting the sensitivity of ECG stress test.

(o) To provide a sensor to be used for the apparatus described herein above.

(p) To provide a disposable sensor for the apparatus described herein above with an adhesive material added to one of the sides of the sensor to bond the sensor to the upper arm. The advantage of using an adhesive sensor is that the sensor remains on a well defined portion of the arm and hence several measurements can be performed without needing to re-position the sensor. This reduces the variations between two measurements as a consequence of a different location of the sensor. A second advantage of using an adhesive sensor is that the sensor remains bonded to the arm in spite of motions of the arm. This reduces the signals resulting from a relative movement between the arm and the sensor. (q) To provide a sensor for the apparatus described herein above, which includes a connector fabricated using standard industrial procedures. The advantage of this is that the cost of the sensor is substantially reduced. (r) To provide a sensor for the apparatus described herein above, which is placed as close to the sensing area as feasible. The advantage of this is that sensing noise is minimized and signal is not attenuated.

Further objects and advantages of our invention will become apparent from a consideration of the drawings and ensuing description.

SUMMARY OF THE INVENTION

There is thus provided, in accordance with a preferred embodiment of the present invention, a non-invasive apparatus for monitoring the cardiac mechanical performance of a patient by measuring the DP/DT, the apparatus comprising: a pressure applying element mountable on a limb of the patient for applying pressure high enough to make a segment of an artery within the limb achieve a collapsed state and partially or totally empty it from blood at least momentarily; a sensor including at least one of a plurality of sensors coupled to said pressure applying element, sensing mechanical changes corresponding to volumetric changes in the artery as the artery progressively recuperates from its collapsed state; a processing unit communicating with said at least one of a plurality of sensors for receiving output corresponding to the mechanical changes from said at least one of a plurality of sensors and computing the velocity of change of the blood pressure wave with respect to time.

DRAWINGS FIG. 1: A view of the left ventricle of the heart showing the left ventricular pressure and the pressure on the artery branching to the upper arm. FIG. 2: Schema showing the arm, with the inflatable cuff encircling the upper arm, the processing unit and an optional monitor for presenting the results,

FIG. 3: A view of the opened cuff, showing the location of the embedded sensors and the air and data connections. FIG. 4: A front (4A) and side (4B) view of the preferred embodiment flexible sensor, showing the structure of the sensor, the deformation sensors, and the connector.

FIG. 5: Two views of the multi-sensor for the preferred embodiment: from above (A) and below (B). The PVDF material is shown together with the connections to the connector. FIG. 6: A view of the protective layer of the preferred embodiment of the multi- sensor, showing the connection to ground.

FIG. 7: A schema of an individual PVDF sensor of the preferred embodiment, showing the way the charges are distributed when the material is subject to deformation. FIG. 8: Schema of the pneumatic circuit of the preferred embodiment of the apparatus, showing the inflatable cuff, the pump and the collection of tubes and valves required for automatically inflating and bleeding. FIG. 9: Schema of the electronic circuit of the preferred embodiment.

FIG. 10: Two views of a scheme of the alternative preferred embodiment based on strain gauge sensors. Views are from above (A) and below (B). FIG. 11: Two different views of the cuff and multi-sensor in relationship with the arm. (A) A side view. (B) A longitudinal cut showing the artery, the tissue and the location of the sensor and the cuff. Fig. 12: Shows the relationship of one of the characteristics of the ECG and the blood pressure pulse. Fig. 13: Shows the relationship between several RQRS pulses of the ECG and the time at which a collapsed brachial artery opens, as a function of applied external pressure. Fig. 14: Pictures an explanation of the method for reconstructing the leading edge of the blood pressure pulse. Fig. 15: Shows how the RQRS pulse can be replaced by the signal of the proximal deformation sensor. Fig. 16: Shows how the DP/DT together with its maximal and averaged value can be computed from the leading edge of the blood pressure pulse.

DETAILED DESCRIPTION

Principle of Operation - - Fig. 1

Fig. 1 sketches the central cardiovascular system, including the left ventricle, the aorta, and an artery bifurcation. Pressure P0(t) denotes the left ventricle pressure while P1(t) denotes the pressure at the aorta exit. The relationship between these two pressures and their timing with respect to the QRS peak is shown in Fig. 5, following the classical study by Hurst, J.W., and Longue R.B.(1970).

When moving from the aorta to the periphery, the pressure wave is further filtered by the cardiovascular system, although the basic parameters of the pressure waveform are maintained at least in large arteries close enough to the aorta, like the brachial artery of the left arm, which is the one used in our invention. Consequently it is possible to determine the DP/DT for the aorta by computing the DP/DT at the say brachial artery.

Preferred Embodiment Sensor — Figs. 2 to 7

A preferred embodiment of the DP/DT monitor of the present invention is illustrated in Fig. 2. The monitor comprises an inflatable cuff 201 mountable on the upper arm 200 of a patient. As detailed herein below, the cuff applies pressure high enough to make a segment of an artery within the arm achieve a collapsed state and empty it from blood at least momentarily. The cuff is adjusted around the arm of the patient by using an auto-adhesive strip 203, such as a Velcro auto-adhesive strip. The cuff is connected by a flexible tube 204 and a cable 205 to the monitor electro-mechanical box 202. The flexible tube is inserted into the box through the pneumatic connection 207. The cable 205 is connected through the connector 208. Externally, 202 has a display 209, an operation button 210 and an external connector 211, such as a USB connector. The box 202 is connected to an external device, such as the personal computer 206 through a cable 212. The external device has two purposes: provide external power supply, and store and further process the data computed by the monitor. Fig. 3 illustrates a closer look at the inflatable cuff 201. In the figure, the cuff is shown extended and with no air. The cuff is inflated by pumping air through the flexible tube 204, and is fixed in place when taking a measurement by using the auto-adhesive strip 203. The cuff has a multi-sensor 306 adhered to its surface. The sensor 306 is adhered by using an adhesive that fixes it in place and can be bent without fracturing. The sensor includes a plurality of deformation sensors 44 as explained in the next paragraph. Figs. 4 to 7 show different views of a sensor with a plurality of deformation sensors. The sensor consists of several layers. Fig. 4 shows all the elements of the sensor, including the sensing elements 44, the connector 43, the covering laminate 40, and the separations 41, 42 providing sensor rigidity and mechanical decoupling between the sensing elements 44. In the preferred embodiment, the sensor is encapsulated into a laminar case 142 mm of length and 35 mm of width. The figure also shows that silver ink coating 45 is used to connect one of the ends of the sensing elements 44 to a pin 46 of the connector 43. The other end of all sensing elements 44 is short circuited and connected to the common pin 47 of the connector 43. The sensing elements and their connection are shown in more detail in Fig. 5. In the preferred embodiment, the sensing elements are fabricated in PVDF (polyvinylidene fluoride), a well-known ferroelectric material which can be customized into the desired form by using standard industrial procedures. As shown in Fig. 7, the PVDF is covered above and below by coats 45U, 45L of silver which collect the charges generated by the PVDF when subject to deformation. The upper coat 45U is connected using a conducting silver path to one of the pins of the sensor. The lower coats 45L corresponding to each sensing unit are connected together to the common pin 47 of the connector. The other end of each sensing element is connected to one pin each of the connector 46. In the preferred embodiment shown iη Fig. 5, six sensing elements are employed. In an alternative embodiment, a different number of sensing elements was used. Each sensing element is 5 mm wide and 29 mm long. The separation between the centers of any two sensing elements is 22 mm, with the center of the element at the other end of the connector is 14 mm from the border of the sensor. Figure 6 shows the Mylar coating used for coating the sensor. The Mylar coating provides strength and heat resistance to the sensor, as well as electrical isolation.

The Pneumatic Circuit - - Fig. 8

Fig. 8 illustrates the pneumatic circuit used for inflating and bleeding the inflatable cuff. The circuit consists of a pump 801 connected to a T-connector through a flexible tube 805. The T-connector is connected to a release valve 806 and to a one-way valve 802. The one-way valve is connected to the external tube 204 through a 4-way connector 809. This connector is also connected to a pressure sensor 803 and a controlled release element 804. The controlled release element is connected to a valve 807.

Electronic Circuit - - Fig. 9

Fig. 9 illustrates the electronic circuit included together with the pneumatic circuit in the electro-mechanical box 202. The circuit includes a data- conditioning and analog-to-digital converter 901 and a micro-controller 902. The signals from the pressure transducer 803 and the multi-sensor 306 are sampled by the analog-to-digital converter included in 901. The resulting digital signals are fed into the micro-controller 902 where the signal processing is performed. The micro-controller also presents the results on the display 304, activates the pump 801 and controls the valves 806 and 807 of the pneumatic circuit. Finally, the micro-controller communicates with the external computer 208 for data downloading and software uploading and with the operation button 210.

Operation - Figs. 8, 9, 11 A and B The manner of operating the DP/DT sensor is identical to that for automatic blood pressure sensors. The micro-controller 902 starts the measurement cycle when the operation button 210 is pressed. The pump 801 is operated with the valve 806 closed and starts inflating the inflatable cuff 201. The micro-controller controls the internal pressure of the cuff by using the pressure sensor 803. When the pressure reaches the specified value for maximum pressure, the pump is stopped and the valve 806 is opened so that the one-way valve 802 closes. A typical value for the high pressure is 190 mmHg, although higher pressures can be used. The micro-controller measures the signals from the sensors 44 and if more than one sensor indicates a reading, then the valve 806 is closed and the cuff is inflated to a higher pressure. Once the cuff is inflated to the sufficiently high pressure, the valve 807 and the cuff starts bleeding air through the controlled release valve 804. This valve is adjusted to release air at a low rate, typically 2 mmHg/sec. When the internal pressure of the cuff reaches a value lower than diastolic blood pressure, typically 50 mmHg, the measurement cycle stops. As shown in Fig. 11, the sensing elements 44 will sense the time instants on which the artery 250 encircled by the cuff recovers from the collapse state. More specifically, Fig. 11 A shows the cuff with the multi-sensor element 306. This multi-sensor is in contact with the arm and covered by the cuff. Fig. 11B shows a sectional view as indicated in Fig. 11 A. The cuff 201 encircles the arm including the artery 250 served by the blood flow 251. Each of the sensing elements 44 are in contact with the arm. Their upper connectors 45U are connected together to a common pin of the cable 205, while each of the lower connectors 45L is connected to a pin of the cable 205. When the cuff 201 is inflated to a sufficiently large pressure, the artery 250 collapses and no blood circulates through it. The proximal sensor, namely the sensor closest to the heart, senses the deformation introduced by the blood as it arrives at the artery located under the extreme of the cuff. If the pressure in the cuff is high enough (typically 190 mmHg as mentioned above) then the remaining sensors will sense a very low signal since blood does not circulate under the cuff. As the cuff bleeds, the pressure inside the cuff reduces and the blood pressure inside the artery under the extreme of the cuff closer to the heart is enough to open the artery during at least a segment of the blood pressure pulse. The sensors 44 sense this opening as a deformation and hence the opening of the arteries can be timed accurately. As explained herein below, this timing is used to reconstruct the leading edge of the blood pressure pulse and from there to derived the DP/DT. The method for measuring the Dp/Dt can be better understood by referring to Fig. 12. As shown in the figure, the pulse waveform is triggered by the QRS peak of the heart, which can be obtained from an ECG. This timing principle has been used before to compute blood pressure. We have discovered that the QRS peak can be replaced by the onset of the pressure wave at the proximal sensor, since there is an approximately constant delay between the QRS and this onset for all internal cuff pressures, at least during a measurement period. For this reason, the pulse obtained by the onset of the pressure wave is referred herein below as reconstructed QRS or RQRS. As explained above, when the pressure inside the cuff is high, the external pressure applied by the cuff is larger than the instantaneous internal pressure of blood inside the artery (i.e., the intramural pressure is negative), the walls of the artery collapse and hence at large cuff pressures no blood circulation occurs. Consequently, if the cuff is inflated to an external pressure, say Pe larger than the diastolic but smaller than systolic pressures, then there will be an almost step change in blood flow downstream the cuff before and after the blood pressure wave reaches the say pressure Pe. Namely, when the instantaneous pressure is less than Pe, then the cuff interrupts the flow of blood and no deformation sensor 44 except for the proximal sensor shows a significant signal. When the instantaneous pressure reaches the say pressure Pe, then the artery opens and blood begins to flow. The flow of blood opens the whole artery passing through the upper arm encircled by the cuff, increasing the cross section under the deformation sensors 44. This is shown in Figure 13 at the point 1310. These changes are detected by the deformation sensors 44 that generate the signals used by the signal processing device. Using the signals from the proximal sensor and the second sensor, the delay time between the two signals t(Pe) is measured. This delay depends on the pressure inside the inflatable cuff Pe. The method for computing DP/DT consists on storing the pairs (t(Pi), Pi) for each one of the heart beats detected by the sensors embedded in the cuff while during the measurement cycle. For simplicity, the time t(Pi) is called ti. The pairs (ti , Pi) are plotted in a graph of pressure vs. time in such a way that the leading edge of the wave pulse is recovered. Figure 14 shows the graph obtained by plotting the pairs (ti, Pi) and the correspondence with the blood pressure peak. The method for measuring DP/DT consists of the following steps: 1. Collect the signals from the sensors 44 embedded in the cuff. 2. Compute the internal pressure P(t) as a function of the time t since the beginning of the measurement cycle. 3. Split the signals from the sensors 44 into intervals corresponding to the individual heart beats during the measurement cycle. This is done by detecting the rising edges of the pulses sensed by the sensors 44 on each heart beat, and using the time instants of these edges to mark the beginning of each one of the intervals mentioned above. 4. Detect the first interval at which a significant signal is obtained from the second sensor, namely, the sensor right after the proximal sensor. In the preferred embodiment, a significant signal is obtained when the peak value reaches 10% of the maximum peak value occurring during the measurement cycle. 5. Starting from the interval detected as explained above, tabulate for each heart beat I, the pressure inside the cuff Pi and the time intervals between the signal in the first sensor and the signal in each one of the remaining sensors: T1i, T2i, T3i and T4i. This is shown in Figure 15. 6. In a preferred embodiment, the time intervals T1i to T4i are measured by detecting the time difference between the onsets of the rise of each pulse signal. It is clear that other methods for measuring the time interval between pulses can be used. 7. In the preferred embodiment, a single time interval Ti is computed by averaging the time intervals between pulses. In an alternative preferred embodiment, only the time interval between the first and the third sensor are used. It is clear that an alternative sensor can be used. 8. The data pairs (Ti, Pi) are the fit using a low order polynomial. In the preferred embodiment, a second order polynomial is used but it is clear that other, higher or lower order polynomials can be used as well. Fitting with a polynomial filters the data and hence reduces the measurement noise. This is shown in Fig. 16. 9. The final step of the method consists of differentiating the polynomial fitted as explained above for computing DP/DT, and computing the maximum of the derivative for computing DP/DT- max.

The method detailed above allows the computation of the Dp/Dt on the leading edge of the blood wave pressure as well as the maximum value of the such velocity, namely Dp/Dt_Max.

ADDITIONAL EMBODIMENTS

An additional embodiment of the multi-sensor is shown in Fig. 10. The alternative embodiment for the disposable sensor uses strain gauge as the basic sensing unit. The sensing unit is now a strain gauge 1004. The upper end of the strain gauge is connected to one of the pins of the connector 1006U by means of the conducting silver path 1005U. The lower end of the strain gauge is connected to the corresponding pin of the connector 1006L by means of the conducting silver path 1005L. Mylar coating is used for coating the sensor. A Mylar coating is also included as shown in Fig. 6, to provide strength and heat resistance to the sensor, as well as electrical isolation.

Claims

C L A I M S: We claim:

1. A non-invasive apparatus, sensor and method for measuring DP/DT, the say apparatus comprising: a pressure applying element mountable on a limb of the patient for applying pressure high enough to make a segment of an artery within the limb achieve a collapsed state and partially or totally empty it from blood at least momentarily; a multi-sensor sensor coupled to said pressure applying element, sensing mechanical changes corresponding to volumetric changes in the artery as the artery progressively recuperates from its collapsed state; processing unit communicating with said multi-sensor sensor for receiving output corresponding to the mechanical changes from said multi-sensor and computing the velocity of variation of blood pressure with respect to time, and the say multi-sensor comprising: a plurality of deformation sensors, consisting of a single layer of material sensitive to deformation, and a collection of conducting wiring to an external connector, and a frame of a harder structure on which the deformation sensors are supported and a layer of a material for isolating the deformation sensor thermally and electrically.

2. The apparatus as claimed in claim 1 wherein said multi-sensor sensing material is a piezoelectric transducers wherein the mechanical changes are determined by measuring changes in the output voltage of the transducers.

3. The apparatus as claimed in claim 1 wherein said multi-sensor sensing material is a stain gauge wherein the mechanical changes are determined by measuring changes in the output voltage of the transducers.

4. The apparatus as claimed in Claim 1, further comprising output means.

5. The apparatus as claimed in Claim 1 , further comprising memory unit.

6. The apparatus as claimed in Claim 1, further comprising means to communicate with a computer, network or a telephone system.

7. The apparatus as claimed in Claims 1, 4, 5 and 6, wherein the processing unit includes algorithm comprising the following steps: a. identification of piezoelectric output pulses with magnitude above certain threshold where at least a pre-determined number of pulses fall within a pre-determined time window; b. determining time differences between the pulses corresponding to same time window and associating to each time difference the pressure of the blood at the say time window; c. approximating the say pair of points with a function of pressure as a function of time, and computing the derivatives of the leading edge of the pressure pulse.

8. The apparatus as claimed in Claim 1 wherein a control system is used to maintain the applied pressure over a period of time substantially at the a determined measurement pressure and the time difference is computed continuously.

9. A method for non-invasive measuring of changes in cardiac mechanical performance of a patient, the method comprising: a. providing a pressure applying element mountable on a limb of the patient for applying pressure enough to make a longitudinal segment of an artery within the limb achieve a collapsed state and empty it from blood at least momentarily; b. providing sensor coupled to the pressure applying element, sensing mechanical changes corresponding to volumetric changes in the artery as the artery progressively recuperates from its collapsed state; c. providing processing unit communicating with the sensor for receiving output corresponding to the mechanical changes from the sensor and computing factors correlated with blood flow and calculate parameters indicating heart performance; d. applying pressure on a portion a limb of a patient through which artery passes enough to collapse the artery preventing at least momentarily the flow of blood through the collapsed artery; e. sensing mechanical changes corresponding to volumetric changes in the artery as the artery progressively recuperates from its collapsed state; f. computing the leading edge of the pressure pulse.

10. The method as claimed in Claim 39, wherein the pressure applied on the portion of the limb of the patient is initially larger than needed to collapse the artery, and wherein it is gradually reduced, sensing the time it takes for the say artery to recover from the collapse state between two consecutive sensors while the pressure is reduced.

11. The method as claimed in Claim 39, further comprising determining a best cuff pressure for considering a measurement, said best pressure is the mean artery pressure or other pressure predetermined relative to the diastolic and systolic blood pressures.

12. The method as claimed in Claim 39, further comprising measuring blood pressure of the patient.

13. The method as claimed in Claim 39, further comprising measuring heart pulse rate of the patient.

14. The method as claimed in Claim 39, carried out continuously over a period of time..

15. The method as claimed in Claim 39, further comprising transmitting data to an external apparatus.

16. The method as claimed in Claim 33, wherein it is incorporated with Holter procedure, in order to detect artifacts and enhance reliability.