DE102024000814A1 - System for determining and monitoring cardiological parameters and procedures - Google Patents

Abstract

A system for determining and monitoring cardiological parameters is described, comprising a pressure sensor device for a medical in vivo application with at least one pressure transducer and an implantable probe with an evaluation circuit connected to the pressure transducer, which is preferably arranged with the pressure transducer in a common extracorporeal housing, and the evaluation circuit is connected to a communication module for the wireless transmission of data from the evaluation circuit to a device for visualizing the signals output by the evaluation circuit, and/or a device for storing the signals output by the evaluation circuit, as well as a method for operating the system.

Description

The invention relates to a system for determining and monitoring cardiological parameters and a method.

Determining blood pressure is one of the most common and widespread methods for recording vital signs in medical diagnosis, therapy, and care. Methodologically, a distinction is made between direct blood pressure measurement and indirect blood pressure measurement.

In direct blood pressure measurement (IBP), also known as invasive or blood-based measurement, a sensor is inserted directly into an artery via an arterial access. Alternatively, access is created to an artery and connected extracorporeally to a sensor. Due to the associated risk of infection and the required equipment infrastructure, the direct intra-arterial method is only used in intensive care, on specially equipped hospital wards, and in the operating room. Indirect, or bloodless, or non-invasive blood pressure measurement (NIBP) uses an electronic blood pressure monitor or a blood pressure cuff and a stethoscope. The values obtained with this method are somewhat less accurate than those obtained with direct blood pressure measurement. Indirect blood pressure measurement is used much more frequently on wards and in doctor's offices and can also be performed by the patient themselves outside of medical facilities.

For example, the WO 2009/115223 An extracorporeal direct blood pressure measurement system with a system element known as a "pressure dome," which derives from the dome-shaped design of the measuring chamber. A sensor, with which such a dome is usually connected for pressure measurement or monitoring, is known as a "transducer," which is understood to be a measuring transducer in a suitable housing that converts the pressures and pressure changes usually transmitted via the pressure dome's membrane into an electrical signal. The membrane in such a dome serves to seal off the blood connection to the patient in an infection-proof manner. The transducer is connected to an electronic diagnostic and monitoring device for displaying or evaluating the measurement signals. The advantage of such an arrangement is the possibility of designing the system element as an inexpensive and easily disposable disposable part, thereby ensuring a hygienically perfect and safe seal of the blood fluid system (see WO 99/37983 A2 .

Extracorporeal systems have the advantage that they can be easily calibrated to ambient pressure by opening the side arm of a three-way stopcock integrated into the extracorporeal line system. Because the room temperature is typically constant in intensive care units or operating rooms, additional measures, such as temperature compensation, are not necessary.

In contrast, implanted pressure transducers have the disadvantage that they are exposed to temperature fluctuations and cannot be zeroed by connection to the environment, i.e. the zero point drift of the implanted pressure transducer must be very close to zero, i.e. remain within the measurement tolerances according to IEC 60601-2-34 even over long periods of months.

Furthermore, implantable pressure transducers are subject to severe limitations regarding the available installation space. For use even in large blood vessels, the transverse dimension of the pressure transducer must generally not exceed approximately 1 mm, as the invasive pressure transducer must not pose an obstacle to blood flow. Therefore, larger designs for compensating for temperature drift are not feasible. Furthermore, the actual pressure transducer circuit must include an electrical isolation barrier, both for a capacitive pressure transducer with at least one movable capacitor plate and for a piezoresistive pressure transducer with a silicon membrane with an etched Wheatstone bridge, which further limits the available installation space.

From the DE 10 2015 116 648 A1 An implantable pressure sensor device with a housing arrangement is known, in which the housing arrangement has outer walls and an inner volume and the housing arrangement comprises at least two pressure transmission membranes, each having a surface and the surfaces are not arranged in a plane. The proposed MEMS chips must be protected in a reactive medium, such as blood. For this purpose, they are typically embedded in an incompressible and inert liquid and hermetically sealed against the reactive medium in a housing. The liquid (e.g. oil) serves as a pressure transmission medium, so that the external pressure can be conducted to the MEMS chip via the housing. Titanium is proposed as a suitable housing material due to its long-term stability and high biocompatibility.

In a patient’s bloodstream, temperature changes of several degrees Celsius can occur, which leads to volume changes in the pressure transmission medium within the housing. Another problem is the temperature change during sterilization, for example using ethylene oxide, where temperature differences of around 30 degrees Celsius occur. The resulting increase in volume and pressure can damage the membranes or the MEMS chip in a conventional pressure sensor housing. Since the housing usually has little compliance or elasticity, the aforementioned volume changes in the pressure transmission medium lead to large pressure fluctuations within the housing. This is due on the one hand to the material properties of the housing and on the other hand to the housing walls, which are relatively thick for the size of the housing. As a result, the pressure measurements of the MEMS chip are falsified because the pressure values to be measured are superimposed by temperature-related pressure fluctuations inside the housing.

In US 8 573 062 B2 For a MEMS chip sensor assembly, the use of a pressure transmission membrane is described, which covers a window that is embedded in the side wall of the housing of the sensor assembly. In US 8 142 362 B2 A pressure transmission membrane arranged on the front side of the housing is described.

In order to provide a pressure sensor device that is largely insensitive to temperature changes in the operating atmosphere and the resulting material stresses, DE 10 2015 116 648 A1 A housing arrangement is proposed that is to have at least two pressure transmission membranes, each having a surface, wherein the surfaces are not arranged in a plane. The use of two pressure transmission membranes creates two non-contiguous surfaces with greater flexibility or elasticity for the housing of the implantable pressure sensor device, so that the pressure inside the housing is sufficiently reduced during temperature fluctuations. Because the two pressure transmission membranes are not arranged in a plane, the stresses and forces on the housing material resulting from volume changes inside the housing can be at least partially compensated, which is intended to increase the robustness of the housing arrangement.

To solve the problem of excessive dimensions in a pressure sensor with integrated temperature compensation, US 2004/0073122 A1 An elongated assembly is proposed, which is sealed at its distal end with an elastic gel plug for pressure transmission. The gel plug is intended to be removable and replaceable by a user and is made of a fully cross-linked multi-component silicone with a precursor and a plasticizer. For some embodiments, it is proposed to cover the gel plug externally with an additional membrane made of a biocompatible material.

To minimize drift, the US 2011/0209553 A1 proposed equipping a piezoresistive pressure sensor with two measuring chambers, one of which is hermetically sealed and has a predetermined reference pressure set in it. Comparative measurements are intended to minimize drift. A similar approach is being taken. Jiachou Wang and ) before.

In the US 2011/0040206 A1 An arrangement with two membranes is proposed, in which one of the membranes is to be electrically deformable for offset compensation.

From the DE 19 19 246 B2 An electrode arrangement for electrical stimulation of the right ventricle is known, comprising a connecting line consisting of an insulating strand and running to a pacemaker, through which an electrical conductor leads to the electrode arranged on the outside of the insulating strand. The insulating strand is intended to be so flexible that its insertion is possible solely through the movement of the heart's bloodstream. This is said to have the disadvantage that electrical conductors that are embedded in the plastic strand so that they cannot be displaced longitudinally are subjected to severe stretching stress when the insulating strand is bent, causing them to tear. This is said to occur particularly easily when the electrode arrangement is retracted slightly to change its position. To prevent the risk of the conductors tearing in such an electrode arrangement, it is proposed to run a tensile-resistant core through the insulating strand. When using two electrical conductors that are not intended to run closely adjacent to one another in a central channel in a tubular strand to avoid parasitic capacitance, the core must be arranged centrally between the conductors for maximum protection. The core is designed to absorb the tensile forces occurring in the insulating material strand. The arrangement between the electrical conductors is designed to allow for different bending capacities of the Insulating material strand in different bending directions can be achieved.

From the DE 000068923703 T2 and the EP 0 417 171 B1 A device for measuring body pressures or physiological pressures is known, which is said to be particularly useful for continuous measurement of pressures. For this purpose, a pressure transmitter catheter device is proposed for transmitting the physiological pressure to a pressure transducer device, which: has a hollow, flexible tube with a first end for arrangement at a location where the physiological pressure is to be measured, and a second end which is in communication with the pressure transducer device, and a liquid which fills the tube and forms a connection with the pressure transducer device, wherein a plug is positioned at the first end in the tube, wherein the plug comprises a material which is capable of transmitting pressure to the liquid, which in turn transmits this pressure to the pressure transducer device.

From the WO 2020/020480 A1 A pressure sensor device is known, having at least one pressure transducer and an implantable probe, wherein the probe is connected proximally to the at least one pressure transducer, the probe further comprises a catheter section and a measuring tip at the distal end of the probe, wherein the probe has a longitudinal extension along the catheter section, wherein the catheter section has at least one lumen for establishing a fluid connection from the measuring tip to the pressure transducer and the lumen is filled with a transmission fluid, wherein the measuring tip comprises a tubular section with at least one laterally arranged opening, wherein the at least one opening is covered by an elastic membrane, and wherein the filling quantity of the transmission fluid is determined such that, at a predetermined temperature of the transmission fluid, the curvature of the membrane transverse to the longitudinal extension is substantially aligned with the contour of the measuring tip transverse to the longitudinal extension. The pressure sensor device described therein has an arrangement that makes it possible to monitor a patient's blood pressure and, in particular, pressure profiles using the implantable probe, without the need for electronic components such as pressure transducers to also be implanted. This significantly reduces the bureaucratic effort involved in manufacturing and using a pressure sensor device according to the invention compared to known implantable pressure measuring devices. Furthermore, the pressure sensor device also makes it possible to monitor the pressure and pressure profiles in a patient while they are being treated with devices that cause strong electrical interference, e.g., an ablation catheter.

It is described as particularly advantageous that the catheter section of the probe with the measuring tip can be implanted into a human or animal body, e.g., into a blood vessel, via a port with only a slightly larger inner diameter. The part of the pressure sensor device containing the pressure transducer and associated electronics can remain outside the body. Such an arrangement allows the advantages of direct blood pressure measurement to be economically combined with the lower regulatory requirements of a passive implant.

The measurement of pressure-volume loops (PV loops) is the gold standard for determining the hemodynamic parameters Ees and Ea. Conductance catheters are the gold standard for measuring PV loops. These are inserted invasively into the ventricle and can simultaneously measure pressure via a pressure sensor and volume via conductance measurement. Alternatively, PV loops can be performed by combining independently performed pressure and volume measurements. Example of this is the measurement of pressure via a right heart catheter and volume via 3D echocardiography or cardiac MRI. The pressure and volume measurements can be performed simultaneously or with a time delay, although simultaneous measurement is ideal. We describe a method for the automated synchronization of arbitrary pressure and volume data based on the leads. This method can be used, for example, to generate pressure-volume loops (PV loops) at the push of a button. An example of this is the use of CorLog data for the pressure signal and 3D echocardiography (3D echo) data for the volume signal. CorLog continuously measures pressure values in the right ventricle. The 3D echo can be used to record the volume curve at specific points. When this occurs, an event marker is set in the system according to the invention. This is used to synchronize the data. If both systems are connected, for example, wirelessly, data transmission can occur automatically as soon as the volume curve has been recorded. One or both of the sensor systems can combine the data into a PV loop.

Continuous pressure and volume curves are roughly synchronized with each other using an event marker. Either both signals have an event marker, or the event marker of one signal is set when the measurement of the other signal starts. Specific physiologically significant points are detected. This is done using the time derivatives of the signals. An example of this could be the opening of the tricuspid valve, indicated by the -/+ zero in the 1st derivative of the volume curve. Starting at the event marker, N beats are selected from the curves. The period of these beats must correspond to a predetermined period Ts. If one of the two sensors already outputs an averaged curve, the period of the averaged curve is used as Ts. Permissible deviations can be specified using an additional parameter dTs. If a suitable beat is found, the respective curve section is saved for later averaging. Once all beats have been found, the individual curve sections are averaged and then displayed as a PV loop.

A method is described for continuously determining the CROSS crossing point from ventricular pressure curves beat by beat. This crossing point can be converted into Pmax, which in turn can be used to calculate variables such as ejection fraction, coupling, stroke volume, as well as Ees and Ea. In contrast to other published methods, the described method does not use regression but calculates CROSS or Piso directly using the first derivative of the pressure signal. This leads to a strict definition of CROSS that is independent of the person performing the measurement. Furthermore, this type of calculation increases the robustness of the algorithm. The method can be applied to left and right ventricular curves. Using Pmax, the isovolumetric pressure curve (Pmax sine curve) can be determined. This can then be used to calculate the difference curve between the isovolumetric and the true pressure curve. The difference between the curves corresponds to the flow and can be used to generate partial flow curves or to determine stroke volume and cardiac output.

• 1 die Druck- und Volumenkurve, die aus der Auswerteschaltung gemäß der vorliegenden Erfindung erhalten wird,
• 2 eine PV-Loop aus Druck- und Volumenkurve gemäß 1,
• 3 ein an einen Patienten angeschlossenes erfindungsgemäßes System mit kontinuierlichem Drucksensor im rechten Ventrikel und gleichzeitiger Messung von 3D-Echokardiographie;
• 4 eine Eventmarke zur groben Synchronisation von Druck- und Volumenkurve nach dem erfindungsgemäßen Verfahren,
• 5 Verwendung der zeitlichen Ableitungen zur Bestimmung von physiologisch bedeutsamen Punkten auf Druck- und Volumenkurve, hier am Beispiel des Öffnens der Trikuspidalklappe,
• 6 die Auswahl von N Zyklen aus Druck- und Volumenkurve. Zyklus muss dabei vorgegebener Periode Ts entsprechen,
• 7 die Bestimmung des Kreuzungspunktes CROSS mit Hilfe der Tangenten an ansteigender und abfallender Flanke der ventrikulären Druckkurve, und
• 8 die Bestimmung des Differenzdrucks HMP(t)-RVP(t) aus den rechtsventrikulären Druckkurven.

The invention is described in more detail with the aid of the accompanying drawings. They show:

• 1 the pressure and volume curve obtained from the evaluation circuit according to the present invention,
• 2 a PV loop of pressure and volume curve according to 1 ,
• 3 a system according to the invention connected to a patient with a continuous pressure sensor in the right ventricle and simultaneous measurement of 3D echocardiography;
• 4 an event mark for the rough synchronization of pressure and volume curves according to the method according to the invention,
• 5 Use of the time derivatives to determine physiologically significant points on the pressure and volume curve, here using the example of the opening of the tricuspid valve,
• 6 the selection of N cycles from the pressure and volume curve. The cycle must correspond to the specified period Ts,
• 7 the determination of the crossing point CROSS using the tangents on the rising and falling flanks of the ventricular pressure curve, and
• 8 the determination of the differential pressure HMP(t)-RVP(t) from the right ventricular pressure curves.

QUOTES CONTAINED IN THE DESCRIPTION

This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 2009/115223 [0004]
• WO 99/37983 A2 [0004]
• DE 10 2015 116 648 A1 [0008, 0011]
• US 8 573 062 B2 [0010]
• US 8 142 362 B2 [0010]
• US 2004/0073122 A1 [0012]
• US 2011/0209553 A1 [0013]
• US 2011/0040206 A1 [0014]
• DE 19 19 246 B2 [0015]
• DE 000068923703 T2 [0016]
• EP 0 417 171 B1 [0016]
• WO 2020/020480 A1 [0017]

Cited non-patent literature

• Jiachou Wang and

Claims (3)

A system for determining and monitoring cardiological parameters, comprising a pressure sensor device for medical in vivo application with at least one pressure transducer and an implantable probe, wherein the probe is proximally connected to the at least one pressure transducer, the probe further comprises a catheter portion and a measuring tip at the distal end of the probe, wherein the probe has a longitudinal extension along the catheter portion, wherein the catheter portion has at least one lumen for establishing a fluid connection from the measuring tip to the pressure transducer, and the lumen is filled with a transmission fluid, wherein the measuring tip comprises a tubular portion with at least one laterally arranged opening, wherein the at least one opening is covered by an elastic membrane, and wherein the filling quantity of the transmission fluid is determined such that, at a predetermined temperature of the transmission fluid, the curvature of the membrane transverse to the longitudinal extension is substantially aligned with the contour of the transverse to the longitudinal extension, wherein the system further comprises a An evaluation circuit is preferably arranged with the pressure transducer in a common, extracorporeal housing, and the evaluation circuit is connected to a communication module for wirelessly transmitting data from the evaluation circuit to a device for visualizing the signals output by the evaluation circuit and/or a device for storing the signals output by the evaluation circuit. Procedure for operating a system according to Claim 1 characterized by the following steps: measurement of continuous pressure curves, determination of defined pressure points using time derivatives, determination of Cross according to the following equation: $$t1=\frac{\left(anti-epad\right)-dpdtmin\ast ejt}{dpdtmax-dpdtmin}$$ $$cross=epad+dpdtmax\ast t1$$ Determination of Pmax from Cross, determination of the Pmax sine curve, determination of the difference between Pmax sine curve and pressure curve, determination of the area of the difference curve for each beat, and determination of hemodynamic parameters such as ejection fraction, stroke volume, elastance, volume, impedance, transmission of the obtained values to the device for visualizing the signals output by the evaluation circuit, and/or a device for storing the signals output by the evaluation circuit. Procedure according to Claim 2 , characterized by calibration with 3D echocardiography.