Devices and methods for determining heart function of a living subject

Abstract

The present invention relates to systems, methods and algorithms for determination of heart pump function and their use in livings subject are described. The invention further relates to complementary parts of such systems that work best in combination. Medical catheters, sheaths and shafts are disclosed that carry an arrangement of integrated digital sensor systems-on-chip (SoC) in the portion thereof residing inside the body. These devices combine at their portion that resides inside the body, the complete chain of signal transduction, signal analog-to-digital conversion and digital signal transmission, and allow to acquire single and multiple physical entities in a single setup. In specific instances the devices integrate wireless data transfer functionality, and in specific instances they integrate wireless energy harvesting for battery-free functionality. The present invention further describes complementary monitor systems that are suited for reception, processing and analysis of data acquired by such catheters/sheaths/shafts to yield a robust assessment of cardiac performance. Moreover, the present invention relates to innovations which render such systems applicable to patients with and without cardiac assist devices.

Claims

1. A medical invasive device that is an elongated sheath configured to receive and guide one of a shaft and a catheter, the medical invasive device comprising: a body portion that is arranged to be inserted into one of a patient's blood vessel, a patient's body cavity, and a patient's body tissue, wherein the body portion incorporates a sensor arrangement and a digital data transmission arrangement; an electronic circuit; and a harvesting unit that includes a receiving coil circuit, the harvesting unit arranged to harvest energy from an electromagnetic field, wherein the electromagnetic field is produced by a number of emitting coil circuits, and wherein an emitting coil circuit has a resonance frequency that is within one of 10% of the resonance frequency of the receiving coil circuit, 1% of the resonance frequency of the receiving coil circuit, and 0.1% of the resonance frequency of the receiving coil circuit.

2. The medical invasive device according to claim 1, wherein the body portion further incorporates an analog-to-digital conversion arrangement.

3. The medical invasive device according to claim 1, further comprising an outside portion that is arranged to be positioned outside a patient's body.

4. The medical invasive device according to claim 1, wherein the electronic circuit comprises a sensor arrangement including a temperature sensor, a pressure sensor, a vibration sensor, an ultrasound sensor, a light sensor, a voltage sensor, or one or more combinations thereof.

5. The medical invasive device according to claim 4, wherein the sensor arrangement comprises at least two sensors for measurement of different physical signals.

6. The medical invasive device according to claim 1, wherein the shaft received and guided is from one of a therapeutic device and a heart pump.

7. The medical invasive device according to claim 1, wherein the body portion has a transversal cross-sectional area of less than one of 60 square millimetres, 20 square millimetres, and 5 square millimetres.

8. The medical invasive device according to claim 1, wherein the electronic circuit comprises a wireless data transmission unit.

9. The medical invasive device according to claim 1, wherein the harvesting unit is arranged to harvest energy from energy sources that are not connected to the medical invasive device by wires.

10. The medical invasive device according to claim 9, wherein the harvesting unit comprises one of a vibration-based power generator and a thermoelectric generator.

11. A medical invasive device that is an elongated sheath configured to receive and guide one of a shaft and a catheter, the medical invasive device comprising: a body portion that is arranged to be inserted into one of a patient's blood vessel, a patient's body cavity, and a patient's body tissue, wherein the body portion incorporates a sensor arrangement and a digital data transmission arrangement; an electronic circuit; and a number of coil circuits arranged to harvest energy from an electromagnetic field in a frequency band selected from one of 5.725 GHz to 5.875 GHz, 2.4 GHz to 2.5 GHz, 902 MHz to 928 MHz, 13.553 MHz to 13.567 MHz, 6.765 MHz to 6.795 MHz, 235 kHz to 275 kHz, and 110 kHz to 205 kHz.

12. A kit comprising: an outer element that is a medical invasive device, the medical invasive device being an elongated sheath configured to receive and guide one of a shaft and a catheter, the medical invasive device comprising: a body portion that is arranged to be inserted into one of a patient's blood vessel, a patient's body cavity, and a patient's body tissue, wherein the body portion incorporates a sensor arrangement and a digital data transmission arrangement; and an electronic circuit; an inner element that is the shaft or the catheter that comprises a coil circuit, wherein the outer element covers at least a segment of the inner element, wherein an inner coil is arranged to transmit energy to the outer element.

13. The kit according to claim 12, wherein at least one of the inner coil is arranged to receive data from the outer element by wireless transmission, and an outer coil is arranged to receive data from an inner element by wireless transmission.

14. A kit comprising an outer element that is a medical invasive device, the medical invasive device being an elongated sheath configured to receive and guide one of a shaft and a catheter, the medical invasive device comprising: a body portion that is arranged to be inserted into one of a patient's blood vessel, a patient's body cavity, and a patient's body tissue, wherein the body portion incorporates a sensor arrangement and a digital data transmission arrangement; and an electronic circuit; an inner element that is the shaft of a percutaneous heart pump that comprises a coil circuit, wherein the outer element covers at least a segment of the inner element.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The medical invasive device according to the present invention, employed in connection with the method of computing cardiac output of a living subject according to the present invention, is described in more detail herein below by way of exemplary embodiments and with reference to the attached drawings, in which:

(2) FIG. 1 is a cross-section of an embodiment of a medical invasive device according to the invention;

(3) FIG. 2 is a side view of an embodiment of a medical invasive device according to the invention;

(4) FIG. 3 represents an embodiment of a sheath with integrated flexible electronics board and receive coil circuit and an embodiment of a shaft with integrated emitter coil circuit according to the invention; and

(5) FIG. 4 is an embodiment of a sheath (outer element) covering a segment of a shaft (inner element) in a coaxial orientation according to the invention.

DETAILED DESCRIPTION

(6) Sensor catheter: In one embodiment of a (C/S/S) according to the present invention, a standalone monitoring catheter was constructed by polymer casting, having 0.018″ inner lumen (intended for a guide wire) and an outer diameter of 2.8 mm, smaller than the sheath of current pulmonary artery catheters. Contained in the polymer cast is a flexible electronics board from polymer with a diameter of 2.4 mm and a length of 15 mm that connects the portion of the device inside the body with the portion outside the body. At its portion inside the body, the flexible board carries two digital sensors in one miniaturized package, namely a digital pressure sensor and a digital temperature sensor, with integrated analog-to-digital conversion and a digital signal transmission, packed into a single plastic body of 2*2*0.76 millimeters (STMicroelectronics, part Nr. LPS22HB), and at the portion outside the body, the flexible electronics board carries a connector for wired readout.

(7) Wireless sensor catheter: In one embodiment of a (C/S/S) according to the present invention, a standalone monitoring catheter was constructed by polymer casting, having 0.018″ inner lumen (intended for a guide wire) and an outer diameter of 2.8 mm, smaller than the sheath of current pulmonary artery catheters. Contained in the polymer cast is a flexible electronics board from polymer with a diameter of 2.4 mm and a length of 15 mm that connects the portion of the device inside the body with the portion outside the body. At its portion inside the body, the flexible board carries two digital sensors in one miniaturized package, namely a digital pressure sensor and a digital temperature sensor, with integrated analog-to-digital conversion and a digital signal transmission, packed into a single plastic body of 2*2*0.76 millimeters (STMicroelectronics, part Nr. LPS22HB), and at the portion outside the body, the flexible electronics board carries miniaturized chips comprising digital communication and wireless transmission (TI) and a small battery (type).

(8) For successful energy harvesting, the energy harvested over time must be sufficient to drive the sensors at the desired measurement intervals (typically ranging between 10 milliseconds to 4 hours) and to drive wireless transmission at its desired transmission intervals (typically ranging between 100 milliseconds to 4 hours).

(9) For inductive, wireless powering of the device, an external electromagnetic field needs to be built up. The requirements for this electromagnetic field include safety, capability for sufficient energy transfer, and compatibility with existing regulation. We have identified several design variants:

(10) 1) a custom designed energy receiving coil on a C/S/S and a matched emitter coil with similar resonant frequency are constructed and optimized such that the received energy is sufficient to drive the electronics integrated in the C/S/S. An example of such a setup is shown in the examples. In a preferred setup, such a combination works in a radiofrequency band that legally permits medical use, and works with a distance from energy emitter to energy receiver that facilitates bedside application, e.g. at 30-50 cm from the catheter insertion site.

(11) 2) an emitting field is created by an emitter in vicinity to the patient bed. Such energy transmission is well known in the field and is, for example, described in detail in the ISO standard 15693 and performs energy transmission and data transmission up to 1-1.5 meters. An advantage of this solution is that clinically desirable distance from the patient is maintained that simplifies patient care; a disadvantage of this solution is that the energy transmitted is low and typically allows only very limited functionality of the electronics on the receiving device.

(12) 3) an emitting field is created by a transmitter put into proximity (up to 10 cm) of the exit site of the device in the skin. Transmission of energy and data is well known in the field and is described in detail in the ISO standard 14443. An advantage of small distance is that the energy yield at the receiver side is improved and thereby allows more functionality on the device side, and a disadvantage is that an emitter coil at this distance from the patient may hinder nursing care of a patient; also, this setup requires that the emitter coil remains in sufficient proximity over time.

(13) 4) an emitting field is created by a transmitter according to a standard for wireless charging, e.g. the Qi standard. The Qi standard is originally intended for high-current charging of devices like mobile phones in close proximity (centimeters) to the emitting coil, but we found that a modified setup can be used that allows a larger distance (up to 1 m) to transfer smaller amounts of energy. While the amount of energy transferred is much smaller (decaying approximately with the cube of the distance), this is still sufficient for the very low-power electronics used in our setup.

(14) 5) an emitting field is created by the catheter crossing a sensor-equipped sheath. This scenario is preferred when the sensor-equipped sheath is used to guide the shaft of a circulatory assist device into the body, thus assuring close proximity of emitting coil and sensor-equipped device and optimizing energy transfer. A working example of this setup is given below.

(15) Other upcoming standards for wireless interaction with transmission of energy and information, e.g. the EPC standard, differ in frequency band, data transmission protocols and other details but can be used wherever specific requirements allow it.

(16) In all options, higher frequencies typically facilitate the design of emitter and receive coils because the desired resonance frequencies can be achieved with lower inductances of coils and smaller capacitors.

(17) Wireless energy transfer/harvesting: In a number of experiments, energy harvesting by coils integrated into our (C/S/S) was tested. To this end, a copper wire receive coil (200 micrometer copper wire, 25 windings, coil diameter 4 mm, coil length 85 mm, inductance estimated by resonant tuning 0.384 microhenry) was integrated into a sheath, cast in PDMS. A resonant circuit was produced by connecting a 1 nanofarad capacitor parallel to the receive coil. Resonance in the receive circuit was observed at the frequency of 8.12 MHz.

(18) In addition, an energy transmit coil was built from 200 micrometer copper wire, 30 windings, coil diameter of 2 mm and coil length of 150 mm, having a measured inductance of 0.377 microhenry. The transmit coil was placed into the shaft of a catheter-based cardiac assist device. A resonant circuit was produced by connecting a capacitor of 1 nanofarad parallel to the emitter coil. Resonance in the emitter circuit was observed practically at the same resonance frequency (8.2 MHz) as in the receive circuit. The shaft was inserted into the sheath so that the emitter coil was positioned coaxially in respect to the receive coil. The emitter circuit connected in serial to a 100 Ohm current-limiting resistor was driven by a sinusoidal signal with frequency of 8.12 MHz and amplitude of 10 V generated by a waveform generator Hewlett Packard 33120A. The receive circuit was connected in serial to a diode TS4148 used for rectification. The rectified signal was fed to a voltage regulator built based on LM3671 step-down DC-DC converter from Texas Instruments.

(19) Successful energy transfer from the emitter circuit to the receiver circuit was documented as follows:

(20) the voltage across a resistive load of 1 kOhm connected to the output of the voltage regulator was 3 V that corresponds to the current of 3 mA and the power of 9 mW. According to the specification of the pressure and temperature sensor LPS22HB and specification of Bluetooth Low Energy (LE) IC nrf52832 from Nordic Semiconductor this power is sufficient for acquisition of the pressure and temperature signals and transmission of the acquired data to a remote Bluetooth LE device.

(21) These results confirm that sufficient energy can be transferred to the energy harvesting, sensor carrying catheter.

(22) Wireless energy transfer/harvesting: In one embodiment of a (C/S/S) according to the present invention, a copper wire receiver coil (200 micrometer copper wire, 20 windings, coil diameter 5 mm, coil length 4 mm, inductance estimated by resonant tuning 1.57 microhenry) was integrated into a sheath, cast in PDMS. A resonant circuit was produced by connecting a 100 picofarad capacitor parallel to the receive coil. Resonance in the receive circuit was observed at the frequency of 12.76 MHz. The emitter coil was separate from the catheter and was implemented with 200 micrometer copper wire, 2 windings, 88 mm coil diameter and coil length 4 mm, having a measured inductance of 1.56 microhenry. A resonant circuit was produced by connecting a 100 picofarad capacitor parallel to the emitter coil. Resonance in the emitter circuit was observed at 12.75 MHz. The emitter circuit connected in serial to a 1 kOhm current-limiting resistor was driven by a sinusoidal signal with frequency of 12.76 MHz and amplitude of 10 V generated by a waveform generator Hewlett Packard 33120A. An SMD1206 red LED was connected in parallel to the receive circuit. Successful energy transfer from the emitter circuit to the receiver circuit was documented as follows: when the emitter coil was positioned in proximity of the receive coil (at a distance of 1-3 mm) the LED started to shine indicating availability of at least several hundred of microwatts of harvested electrical power according to LED specification.

(23) Wireless, energy harvesting sensor catheter: In one embodiment of a (C/S/S) according to the present invention, an access sheath for a catheter-based cardiac assist device was constructed by polymer casting, having an inner open lumen of 2.8 mm and an outer diameter of 4 mm, corresponding to the size requirements for access sheaths of the cardiac assist device. Contained in the polymer cast is a flexible electronics board from polymer with a diameter of 3 mm and a length of 15 mm that connects the portion of the device inside the body with the portion outside the body. At its portion inside the body, the flexible board carries two digital sensors in one miniaturized package, namely a digital pressure sensor and a digital temperature sensor, with integrated analog-to-digital conversion and a digital signal transmission, packed into a single plastic body of 2*2*0.76 millimeters (STMicroelectronics, part Nr. LPS22HB), and at the portion outside the body, the flexible electronics board carries miniaturized chips comprising digital communication, wireless transmission and energy harvesting (TI).

(24) The present disclosure also comprises the following further embodiments:

(25) Embodiment 1 is a medical invasive device having a body portion arranged to be inserted into one of, a blood vessel, a body cavity and a body tissue, that is equipped with an electronic circuit and that incorporates in the body portion a sensor arrangement and a digital data transmission arrangement.

(26) Embodiment 2 is the medical invasive device of embodiment 1, having an analog-to-digital conversion arrangement in its body portion.

(27) Embodiment 3 is the medical invasive device of the embodiment 1 or of the embodiment 2, wherein the medical invasive device has an outside portion arranged to be positioned outside the body.

(28) Embodiment 4 is the medical invasive device of any one of the embodiments 1 to 3, whereby the electronic circuit comprises a sensor arrangement having a temperature sensor, a pressure sensor, a vibration sensor, an ultrasound sensor, a light sensor, a voltage sensor or any combination thereof.

(29) Embodiment 5 is the medical invasive device of any one of the embodiments 1 to 4, whereby the sensor arrangement comprises at least two sensors for measurement of different physical signals.

(30) Embodiment 6 is the medical invasive device of any one of the embodiments 1 to 5, whereby the sensor arrangement comprises at least three sensors for measurement of different physical signals.

(31) Embodiment 7 is the medical invasive device of any one of the embodiments 1 to 6, wherein the medical invasive device has a shaft being an elongated object that carries the body portion and being arranged to traverse the skin level.

(32) Embodiment 8 is the medical invasive device of any one of the embodiments 1 to 7, wherein the medical invasive device is a catheter that is an elongated object arranged to enter the body and comprises a number of fluid columns.

(33) Embodiment 9 is the medical invasive device of any one of the embodiments 1 to 8, wherein the medical invasive device is a sheath that is an elongated object arranged to guide one of, a catheter, a shaft of a therapeutic device, and a shaft of a heart pump.

(34) Embodiment 10 is the medical invasive device of any one of the embodiments 1 to 9, wherein the body portion has a transversal cross-sectional area of less than 60 square millimetres.

(35) Embodiment 11 is the medical invasive device of any one of the embodiments 1 to 10, wherein the body portion has a transversal cross-sectional area of less than 20 square millimetres.

(36) Embodiment 12 is the medical invasive device of any one of the embodiments 1 to 11, wherein the body portion has a transversal cross-sectional area of less than 5 square millimetres.

(37) Embodiment 13 is the medical invasive device of any one of the embodiments 1 to 12, whereby the electronic circuit comprises a wireless data transmission unit.

(38) Embodiment 14 is the medical invasive device of any one of the embodiments 3 to 13, whereby the outside portion comprises a wireless data transmission unit.

(39) Embodiment 15 is the medical invasive device of embodiment 14, whereby the wireless data transmission unit is disconnectable from a base of the outside portion.

(40) Embodiment 16 is the medical invasive device of any one of the embodiments 1 to 15, powered by one of, a battery and a capacitor.

(41) Embodiment 17 is the medical invasive device of any one of the embodiments 3 to 16, wherein a battery or a capacitor are disconnectable from the outside portion.

(42) Embodiment 18 is the medical invasive device of any one of the embodiments 1 to 17, whereby the electronic circuit comprises a harvesting unit arranged to harvest energy from energy sources that are not connected to the medical invasive device by wires.

(43) Embodiment 19 is the medical invasive device of any one of the embodiments 3 to 18, whereby the outside portion carries a harvesting unit.

(44) Embodiment 20 is the medical invasive device of embodiment 19, wherein the harvesting unit comprises a coil for harvesting electromagnetic energy.

(45) Embodiment 21 is the medical invasive device of any one of the embodiments 19 or 20, wherein the harvesting unit comprises a solar cell.

(46) Embodiment 22 is the medical invasive device of any one of the embodiments 18 to 21, wherein the harvesting unit comprises a vibration-based power generator.

(47) Embodiment 23 is the medical invasive device of any one of the embodiments 18 to 22, wherein the harvesting unit comprises a thermoelectric generator.

(48) Embodiment 24 is the medical invasive device of any one of the embodiments 1 to 23, comprising a harvesting unit with a receiving coil circuit that is tuned to a frequency such that an electromagnetic field typically produced in its proximity elicits an energy transfer to the coil that is sufficient to drive the electronic circuit on the body portion and optionally any other electronic circuits of the medical invasive device.

(49) Embodiment 25 is the medical invasive device of any one of the embodiments 1 to 24, comprising a harvesting unit with a receiving coil circuit arranged for energy harvesting from an electromagnetic field, whereby the field is produced by a number of emitting coil circuits, and whereby an emitting coil circuit has a resonance frequency within 10% of the resonance frequency of the receive coil circuit, and preferably within 1% of the resonance frequency of the receive coil circuit, and particularly preferably within 0.1% of the resonance frequency of the receive coil circuit.

(50) Embodiment 26 is the medical invasive device of any one of the embodiments 1 to 25, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging from 5.725 to 5.875 GHz.

(51) Embodiment 27 is the medical invasive device of any one of the embodiments 1 to 26, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging from 2.4 to 2.5 GHz.

(52) Embodiment 28 is the medical invasive device of any one of the embodiments 1 to 27, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging from 902 to 928 MHz.

(53) Embodiment 29 is the medical invasive device according to any one of the embodiments 1 to 28, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging 13.553 to 13.567 MHz.

(54) Embodiment 30 is the medical invasive device according to any one of the embodiments 1 to 29, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging from 6.765 to 6.795 MHz.

(55) Embodiment 31 is the medical invasive device according to any one of the embodiments 1 to 30, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging from 235 to 275 kHz (Power Matters Alliance (PMA) defined band).

(56) Embodiment 32 is the medical invasive device according to any one of the embodiments 1 to 31, comprising a number of coil circuits arranged for energy harvesting from an electromagnetic field in the frequency band ranging from 110 to 205 kHz (Wireless Power Consortium (WPC) defined band).

(57) Embodiment 33 is a kit comprising an outer element that is a sheath according to one of the embodiments 9 to 32, and an inner element being a shaft or a catheter that comprises a coil circuit, whereby the outer element covers at least a segment of the inner element.

(58) Embodiment 34 is a kit according to embodiment 33, whereby the inner element is arranged to be in a coaxial orientation relative to the outer element.

(59) Embodiment 35 is a kit according to embodiment 33 or 34, wherein an inner coil is arranged to transmit energy to the outer element.

(60) Embodiment 36 is a kit according to embodiment 35, wherein the inner coil is arranged to receive data from the outer element by wireless transmission.

(61) Embodiment 37 is a kit according to any one of embodiments 33 to 36, wherein an outer coil is arranged to receive data from the inner element by wireless transmission.

(62) Embodiment 38 is a kit according to any one of embodiments 33 to 37, wherein the inner element is the shaft of a percutaneous heart pump.

(63) Embodiment 39 is a method of computing cardiac output (CO) of a living subject, wherein a mathematical model is constructed that links an input data vector with a target CO value.

(64) Embodiment 40 is the method of embodiment 39, wherein said mathematical model is nonlinear.

(65) Embodiment 41 is the method of embodiments 39 or 40, wherein said input data vector comprises at least one sensor measurement acquired by a medical invasive device according to any of the embodiments 1 to 32.

(66) Embodiment 42 is the method of any one of embodiments 39 to 41, wherein said input data vector comprises physiologic input source data from said living subject.

(67) Embodiment 43 is the method of any one of embodiments 39 to 42, wherein said input data vector comprises the area under the curve of a repeated temperature measurement.

(68) Embodiment 44 is the method of any one of embodiments 39 to 43, wherein said input data vector comprises the area under the curve of a repeated temperature measurement after injection of a bolus of fluid into the venous circulation, whereby said injected bolus has a temperature different from the blood temperature.

(69) Embodiment 45 is the method of any one of embodiments 39 to 44, wherein said input data vector comprises numbers derived from arterial pulse pressure analysis.

(70) Embodiment 46 is the method of any one of embodiments 39 to 45, wherein said input data vector comprises numbers derived from arterial pulse pressure analysis, whereby said number is one of, beat-to-beat interval, beat rate, systolic pressure, diastolic pressure, pulse pressure, peak systolic pressure difference per time difference, area under the pulse curve and area under the systolic portion of a pulse pressure wave.

(71) Embodiment 47 is the method of any one of embodiments 39 to 46, wherein said input data vector comprises at least one of: systolic pressure of said living subject, diastolic pressure of said living subject, and pulse pressure of said living subject.

(72) Embodiment 48 is the method of any one of embodiments 39 to 47, wherein said input data vector comprises at least one of: age of said living subject, gender of said living subject, height of said living subject, weight of said living subject, and temperature of said living subject.

(73) Embodiment 49 is the method of any one of embodiments 39 to 48, wherein said input data vector comprises at least one of: cardiac pump type, cardiac pump performance setting, cardiac pump size, cardiac pump blood flow, cardiac pump rotation speed, cardiac pump power consumption, cardiac pump electrical current consumption, cardiac pump pressure sensor reading.

(74) Embodiment 50 is the method of any one of embodiments 39 to 49, wherein said target CO value is determined by an algorithm that comprises determining the area under the curve of a temperature measured repeatedly at multiple time points.

(75) Embodiment 51 is the method of any one of embodiments 39 to 50, wherein the target CO value is determined by analysis of physiological signals measured by a medical invasive device according to any of the embodiments 1 to 32.

(76) Embodiment 52 is the method of any one of embodiments 39 to 51, whereby generating the mathematical model comprises fitting said input data vector into said target CO value in a least-square optimal fashion.

(77) Embodiment 53 is the method of any one of embodiments 39 to 52, whereby generating the mathematical model comprises training of an artificial neural network (ANN).

(78) Embodiment 54 is the method of any one of embodiments 39 to 53, whereby generating the mathematical model comprises unsupervised training of a deep neural network (DNN).

(79) Embodiment 55 is the method of any one of embodiments 39 to 53, whereby generating the mathematical model comprises supervised training of a deep neural network (DNN).

(80) Embodiment 56 is the method of any one of embodiments 39 to 55, whereby generating the mathematical model comprises training of a deep believe network (DBN).

(81) Embodiment 57 is the method of any one of embodiments 39 to 56, comprising: obtaining an input data vector; transforming said input data vector using at least said mathematical model; and expressing a result of said transformation as a CO value in physiologic units.

(82) Embodiment 58 is the method of any one of embodiments 39 to 57, comprising: obtaining a plurality of said target CO values; generating said mathematical model based at least in part on said target CO values; obtaining an input data vector; transforming said input data vector using at least said mathematical model; and expressing a result of said transformation as a CO value in physiologic units.

(83) Embodiment 59 is an apparatus comprising an arrangement to receive data transmitted by a medical invasive device according to any one of the embodiments 1 to 32.

(84) Embodiment 60 is the apparatus of embodiment 59, wherein data are wirelessly transmitted by the medical invasive device.

(85) Embodiment 61 is the apparatus of embodiment 59 or 60, comprising an arrangement to receive data, used for derivation of the input data vectors, transmitted from a second apparatus.

(86) Embodiment 62 is the apparatus of embodiment 61, whereby the second apparatus is a medical monitor, defined as a device that is arranged to be placed in the same room as a patient and comprises a display arranged to display vital signs of said patient.

(87) Embodiment 63 is the apparatus of embodiment 61 or 62, whereby the second apparatus is the control device of a heart pump.

(88) Embodiment 64 is the apparatus of any one of embodiments 61 to 63, comprising an arrangement to receive data, used for derivation of the input data vectors, transmitted wirelessly from the second apparatus.

(89) Embodiment 65 is the apparatus of any one of embodiments 60 to 64, whereby the wireless data transmission follows one of, the WiFi standard, the Bluetooth standard, the Ants standard.

(90) Embodiment 66 is a computer program comprising a code structure arranged to implement a method according to any one of embodiments 39 to 58 when being executed on a computer.

(91) Embodiment 67 is the apparatus according to any one of embodiments 59 to 65, comprising a computer program according to the embodiment 66.

(92) Embodiment 68 is the apparatus according to any of embodiments 59 to 65 and to embodiment 67, comprising a display arranged to display at least cardio output (CO).

(93) Embodiment 69 is the computer program according to embodiment 66, stored on a computer readable medium.

(94) Embodiment 70 is a computer program product stored on a machine readable carrier, comprising program code means to implement a method according to any one of embodiments 39 to 58 when being executed on a computer.