Auxiliary artificial heart

Abstract

To provide excellent assist to a patient's circulatory system.SOLUTION: A control device (100) which controls a rotary speed (nVAD(t)) of a non-beating type auxiliary artificial heart, namely VAD (50), and which uses an event based in-beat control strategy is configured so that, the rotary speed of the VAD is changed in a cardiac cycle of a heart to be assisted, and the change of the rotary speed is synchronized with the heart beat by at least one series of trigger signals (σ(t)) related to at least one in-cardiac cycle prescribed feature event, and the control device (100) is provided on a VAD(50) for heart assist for controlling preferably, for example, the VAD being a catheter based blood pump, in a non-beat rotation system.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] The present invention relates to the field of non-pulsatile ventricular assist devices (VADs), and in particular to a control device for intrapulsatile control of a non-pulsatile VAD, such as an intravascular rotary blood pump, and a VAD equipped with such a control device for controlling the VAD itself. [Background technology]

[0002] When a patient's heart pumps poorly despite appropriate medical treatment, a VAD can assist the circulatory system. By providing a parallel supply of blood to the ventricles of the heart, a VAD can assist or even replace the inadequate ventricular pumping function of the heart. With this goal in mind, a VAD is usually designed to take blood from the blood circulation at the inlet and return or eject blood back into the blood circulation at the outlet. To do this, the VAD must overcome the pressure difference between the outlet and inlet, i.e. the pressure difference across the VAD's load.

[0003] One specific example of a VAD is a catheter-type rotary blood pump that is designed to be placed directly or implanted in the heart for hours or days to assist cardiac function until recovery. Patent Document 1 discloses an example of an intravascular rotary blood pump. However, other types of VADs also exist.

[0004] Patients receiving cardiac support with nonpulsatile blood pumps have an increased tendency to bleed, which appears to be related to a deficiency of a specific blood glycoprotein known as von Willebrand factor (vWF), which is involved in bleeding.

[0005] The term "cardiac cycle" as used herein encompasses the dynamic cardiac behavior during one heartbeat, e.g., blood pressure and ventricular volumes over time. The definition of a heartbeat as used herein is one that begins with the elicitation of an atrial contraction and ends immediately prior to the subsequent atrial contraction, and is divided into systole and diastole. Systole (also called the ejection phase of the heart) is the phase between mitral and aortic valve closure. Diastole (also called the filling phase of the heart) is the phase between aortic and mitral valve closure. The frequency with which the heart goes through a cardiac cycle is known as the heart rate. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] U.S. Patent No. 5,911,685 (A) [Non-patent literature]

[0007] [Non-Patent Document 1] RD Mosteller, “Simplified calculation of body-surface area”, N. Engl. J. Med. 317, No. 17, October 1987, p. 1098 [Non-Patent Document 2] Catanho et al., “Model of Aortic Blood Flow Using the Windkessel Effect”, Beng 221, Mathematical Methods in Bioengineering, Report, 2012 Summary of the Invention [Problem to be solved by the invention]

[0008] It is an object of the present invention to provide a superior support for the circulatory system of a patient, which avoids or at least reduces the above-mentioned vWF deficiency.

[0009] In particular, it is an object of the present invention to provide an intelligent control device for a VAD, such as a rotary blood pump, which operates the VAD in a manner aimed at avoiding or at least reducing the side effects and thus vWF deficiency due to the application of non-pulsatile VADs.

[0010] In particular, it is a further object of the present invention to provide an intelligent control device for a VAD that operates the VAD to achieve the required blood pressure associated with the patient's current perfusion needs while avoiding or at least reducing side effects associated with the application of a non-pulsatile VAD. [Means for solving the problem]

[0011] The inventors have found that when minimal residual pulsatility of blood pressure is restored and / or maintained in the circulatory system, the increased bleeding tendency noted above is small, and in addition, sufficient pressure pulsatility is also likely to support adequate perfusion of the microvasculature of the circulatory system.

[0012] That is, the main idea of ​​the present invention is to achieve a predetermined desired minimum pulsatility by an event-based intra-beat control strategy, in particular by expanding the VAD rotational speed control loop with a speed command signal generator that generates a speed command signal to vary the VAD rotational speed, and to achieve this according to a first mechanism by open loop control, in particular a mechanism that varies the speed command signal between predetermined rotational speed levels, or a second mechanism by closed loop pressure control in a feedback system, in particular a mechanism that automatically sets the speed command signal for each heartbeat by an additional outer pressure control loop to perform cascade control.

[0013] The proposed event-based intrapulsatile blood pressure control strategy, according to a specific embodiment, allows for varying the blood flow within the VAD within the cardiac cycle to affect the pulsatility of the patient's blood pressure. One specific application of this event-based intrapulsatile blood pressure control strategy would be to restore and / or maintain a desired minimum pulsatility of the arterial blood pressure, thereby avoiding a postulated side effect of VAD application on vWF release. In support of this, the fact that many continuous flow VADs have been observed to have reduced pulsatility and thus reduced vWF appearance.

[0014] Thus, the proposed event-based intra-pulsatile control strategy for VAD rotation speed is particularly useful for avoiding the inherent side effects of non-pulsatile VADs that are related to vWF deficiency. In other words, the proposed speed modification to restore and / or maintain a desired minimum blood pressure pulsatility is not considered a cure, but rather a means to eliminate the inherent side effects of non-pulsatile VADs.

[0015] Furthermore, varying the pump speed within the cardiac cycle (hereinafter also referred to as "heart beat" or "beat") has other beneficial effects in contrast to non-pulsatile cardiac assistance, such as improved perfusion of the microvasculature of the circulatory system.

[0016] The term "pulsatility" in the context of restoring and / or maintaining a desired minimum pulsatility of arterial blood pressure generally refers to the maximum aortic pressure AoP| during the hth cardiac cycle. max (h) Minimum aortic pressure AoP| min (h) Difference between ΔAoP(h)=AoP| max (h)-AoP| min (h) It is understood that this refers to the following.

[0017] In the following, for the sake of simplicity, the characteristic measurements and calculations will be referred to exclusively at the respective (j-1), j, (j+1) etc. heart beats, more generally at the h-th heart beat, thereby also including the dependence of the values ​​on the successive time t and for the respective measurement point k. For example, AoP|max (j)=max k {AoP(t j,k )} where k=0,…,m j In the above, the jth heartbeat is indicated by the index j, and the maximum value of the signal AoP relating to the jth heartbeat is measured from the first measurement point k=0 of the jth heartbeat to the final measurement point k=m just before the start of the next (j+1)th heartbeat. j Ending with k=0,…,m j The calculation is based on the measured signal AoP values ​​for all the AoP| max (j+1)=max k {AoP(t j+1,k )} where k=0,…,m j+1 And so on.

[0018] The inventors have envisaged that restoring and / or maintaining a minimum residual pulsatility is desirable, particularly in the case of a circulatory system supported by a VAD. Therefore, the main idea of ​​the present invention is to determine the rotational speed n of the VAD within a cardiac cycle, i.e., within one cardiac beat. VAD (t) is changed, and the desired minimum pulsatility ΔAoP ~ (h) and focuses on improving the control of non-pulsatile VADs so that the focus is on restoring and / or maintaining minimal residual pulsatility in the artery, e.g., the aorta in the case of left ventricular assist. The definitions of the various pulsatility are as follows: Physiological (unassisted) pulsatility: ΔAoP(h)=AoP| max (h)-AoP| min (h) Desired (assisted) minimum pulsatility: ΔAoP ~ (h)=AoP ~ | max (h)-AoP ~ | min (h) Pulsatile difference: ΔAoP pulse (h)=ΔAoP ~ (h)-ΔAoP(h) (See also FIG. 3a; in this application, ~ " means a wavy line above the AoP).

[0019] Thus, the desired minimum pulsatility ΔAoP ~ (h) is the maximum and minimum desired aortic pressure AoP during the hth cardiac cycle. ~ | max (h), AoP ~ | min (h) depends on the pulsatility difference ΔAoP pulse (h) is the current physiological (unassisted) pulsatility ΔAoP(h) and the desired (assisted) minimum pulsatility ΔAoP ~ (h) is defined to be the difference between

[0020] In this regard, the inventors have further found that the predetermined value for the desired minimum pulsatility is ΔAoP ~ (h)=[15,…,30]mmHg but within the range of desired minimum pulsatility ΔAoP ~ It is acceptable for (h) to be higher.

[0021] The inventors have further found that a physical requirement that should preferably be met by a VAD used in the applications disclosed herein is the lack of significant inertia, i.e., it is desirable for the VAD to be a low inertia device. Currently, rotary blood pumps, such as the catheter-type pumps mentioned above, which have a negligible mass moment of inertia, are perfectly suited for speed control scenarios with intra-pulse speed changes, and are highly energy efficient, avoiding, for example, heat losses. Suitable characteristics for achieving a VAD exhibiting a low mass moment of inertia include, among other things, but not limited to, the low mass of the moving parts, particularly the rotating parts, of the VAD, e.g., the rotor or impeller may be manufactured from lightweight materials, e.g., plastic, composite materials, etc., the drive means, e.g., an electric motor, being located close to, preferably in close proximity to, and most preferably adjacent to, the rotor or impeller so that the shaft connecting the motor to the rotor or impeller can be kept short and the rotating mass kept low (e.g., devices are known which have a rotary drive cable or wire connecting the rotor to the motor, but this may be undesirable as the mass of the cable or wire increases the mass to be accelerated and decelerated), and the small diameter of the moving parts, e.g., the rotating parts, so that the mass moments of inertia of those parts can be kept low.

[0022] In a first aspect of the present invention, the rotation speed (hereinafter simply referred to as "speed") n VAD A controller is provided that varies (t) within the cardiac cycle in an event-based manner with reference to physiological conditions.

[0023] With this in mind, the control device is adapted to vary the rate of the VAD within a cardiac cycle of the assisted heart and, in cooperation with the trigger signal generator, generate a rate command signal n for the rate using at least one event sequence relating to at least one predetermined characteristic recurrent event within the cardiac cycle. VAD The change in (t) can be configured to be synchronized with the heart rate, thereby allowing the VAD-induced blood flow Q to be synchronized with the intrinsic cardiac output of the assisted heart. VAD (t) can have an effect.

[0024] According to a specific embodiment, the control device is configured to control a predetermined pulse duration τ pulse (h) or heart rate dependent pulse duration τ assist (h) Basic speed level n VAD set,basic Based on (h), the speed reference signal n VAD set (t) so that the desired minimum pulsatility ΔAoP(h)=ΔAoP(t) due to the blood flow provided in the VAD in the hth cardiac cycle is ~ (h) can be configured to occur within the artery of interest.

[0025] If the VAD is configured for left ventricular assist, then at least the aorta will be the artery of interest. Alternatively, if the VAD is configured for right ventricular assist, then at least the pulmonary artery will be the artery of interest.

[0026] To achieve this, the controller is adjusted to match the VAD reference signal n VAD set (t) and adjust the VAD speed n by the first mechanism or the second mechanism. VAD (t) to control the desired minimum pulsatility ΔAoP ~ It should be configured to achieve (h).

[0027] The control device in the form of a first mechanism receives a speed command signal n in an open loop manner, for example by a command signal generator. VAD set According to a first mechanism, an event-based command signal generator is used to adjust the VAD speed command signal n (t) between predetermined speed levels. VAD set (t) and thereby the desired minimum pulsatility ΔAoP ~ (h) can be generated.

[0028] The control device in the form of the second mechanism may, for example, control the speed n of the VAD. VAD By extending the speed control loop associated with (t) with an additional pressure control loop, resulting in a cascade control strategy, the speed reference signal n is calculated according to a closed-loop feedback scheme. VADset According to the second mechanism, the speed command signal n is adjusted by a speed command signal generator using a feedback pressure control strategy, for example, by an outer loop. VAD set By automatically setting (t), the desired minimum pulsatility ΔAoP for the h-th heartbeat is obtained while taking into account physiologically induced boundary conditions. ~ (h) can be realized. The first mechanism may take into account physiologically induced boundary conditions.

[0029] Examples of such boundary conditions are limits on the available blood volume and / or the mean arterial blood pressure AoP - (h) may be the maximum and / or minimum level (referred to herein as " - (" means a horizontal line over the AoP). In a controller operating within these physiological constraints, it is desirable to monitor ventricular filling pressure (e.g., with a pressure sensor within the ventricle) and potential aspiration events resulting from a lack of blood volume (e.g., with a pressure sensor located at or within the VAD inlet to monitor aspiration-related negative inlet pressure).

[0030] Speed ​​command signal n VAD set Both the open-loop mechanism (first mechanism) and the closed-loop mechanism (second mechanism) for generating (t) may be configured to operate in an event-based manner, and both aim to generate a pulse of a predetermined pulse duration τ pulse (h) VAD speed reference signal n VAD set (t) to determine the desired minimum pulsatility ΔAoP within the hth heartbeat. ~ (h) can be placed in generating.

[0031] The control device controls the VAD speed n VAD The VAD speed command signal n may be configured with an inner control loop for controlling (t) and an outer loop having a structure based on the above-mentioned first or second mechanism. The inner (speed) control loop can use a general high-speed feedback closed loop control. VAD setWe focus on the generation of (t) for the inner control loop.

[0032] Preferably, the control device controls the speed command signal n by using at least one sequence of trigger signals (σ(t)) related to at least one predetermined cardiac cycle characteristic event. VAD set Adjustment of (t), for example, may be configured to synchronize the start and / or end of a command signal pulse with the heart rate.

[0033] For example, the control device may be VAD set (t) to increase the portion of the intra-arterial blood pressure of interest contributed by the VAD at a given time during the cardiac cycle. In general, the controller generates a rate command signal n VAD set (t) may be configured to be set to a high level during systole and / or a low level during diastole.

[0034] For example, the desired minimum pulsatility may be generated by only changing the systolic speed of the assisted heart. VAD set (t) is expressed as a time period before, at, or shortly after the onset of systole of the assisted heart, at a basal rate level n VAD set (t)=n VAD set,basic (h) to target speed level n VAD set (t)=n VAD set,basic (h) + Δn VAD set (h) and then adjust it to the base rate level n before, at or shortly after the end of the systole. VAD set,basic (h) and then lower it again. In this way, the basic speed level n VAD set,basic Speed ​​difference Δn in (h) VAD set Adding and increasing (h) produces a positive rate pulse during systole of the assisted heart.

[0035] Similarly, the desired minimum pulsatility may be generated by only rate changes during diastole of the assisted heart. VAD set (t) is adjusted to the base rate level n before, at, or shortly after the onset of diastole of the assisted heart. VAD set,basic (h) to target speed level n VAD set (t)=n VAD set,basic (h)-Δn VAD set (h) to the base rate level n before, at or shortly after the end of diastole. VAD set,basic The speed level can be increased again to (h). In this way, the basic speed level n VAD set,basic From (h), the speed difference Δn VAD set Decreasing (h) produces a negative rate pulse during diastole of the assisted heart.

[0036] However, either speed command changes during systole or diastole are common examples of synchronizing speed variations to the heart rate. As can be seen, by combining both positive speed pulses during systole and negative speed pulses during diastole, the desired minimum pulsatility ΔAoP ~ (h) may be generated.

[0037] Note that the reason for synchronizing the rate command modification with the cardiac cycle is the enhancement of the residual pulsatility of the failing heart, which comes from the natural heart contraction during systole. What is desired is for the rate command modification to generate a systolic flow contribution to the natural ejection of the heart alone, i.e., co-ejection by the heart and the VAD.

[0038] Therefore, in the first embodiment, the control device is configured to control the speed command signal n VAD set By adjusting the VAD speed by changing (t), the VAD-induced blood flow Q VAD(t) is configured to substantially decrease during the diastole of the cardiac cycle and / or to substantially increase during the systole of the cardiac cycle, thereby restoring and maintaining a desired minimum pulsatility of arterial blood pressure. Slowing the diastolic velocity of the VAD will allow adequate filling of the ventricle and thus systolic co-ejection of blood from the VAD and the native heart.

[0039] The inventors have discovered that by optimizing the generation of adequate peak systolic flow rates for both the native heart and the VAD for purposes of rate command signal modification, the total peak beat-to-beat flow rate can be increased. Q total | max (h)=Q heart | max (h)+Q VAD | max (h) and total ejection volume per heartbeat (EV) EV(h) = EV heart (h)+EV VAD (h) This can cause an appropriate increase in systolic systemic blood pressure. The natural heart's co-ejection function can depend on the ventricular preload, the level of ventricular filling and the level of cardiac contractility, as well as the achievable peak flow of the VAD. The natural heart's co-ejection function can also depend on the patient's obesity index, or body surface area, or vascular compliance, as well as peripheral resistance.

[0040] For example, a typical patient with a height of 1.75 m and weight of 75 kg has an average blood flow of approximately 5 L / min. The requirement can be estimated from the human body surface area (BSA). The body surface area of ​​this typical patient is approximately 1.9 m. 2 (Based on the formula from Non-Patent Document 1). Normal blood flow is normalized by this BSA to 2.6 L / m 2 With an average blood flow of 5 L / min, a healthy person at rest has a blood pressure of approximately 120 mmHg to 80 mmHg.

[0041] Total peak systolic flow Q total | maxIf (h) is about 8L / min, a normal-sized human (BSA is 1.9m 2 ) with a desired minimum pulsatility ΔAoP of approximately 15 mmHg ~ (h). More generally, therefore, a total peak flow of 8 L / min is considered sufficient to provide a 2 Dividing by and multiplying by the patient's actual BSA will give a more patient-specific peak flow value. 2 In patients with ~ (h) is the appropriate total peak systolic flow Q total | max More generally, taking into account all the variations in compliance and peripheral resistance, a total peak flow of 6 L / min to 10 L / min would be sufficient to achieve at least ΔAoP ~ (h) should be sufficient to obtain a target desired minimum pulsatility of ≥ 15 mmHg. Therefore, Q toal | max (h)=Q heart | max (h)+Q VAD | max (h)>6L / min,…,10L / min The total peak flow, and therefore EV(h) = EV heart (h)+EV VAD (h)=40ml,…,70ml It is desirable to have a peak systolic flow velocity that results in a total ejection volume that is equal to or greater than the desired minimum pulsatility ΔAoP ~ (h) >[15,…,30] mmHg can be achieved.

[0042] Desired minimum pulsatility ΔAoP ~(h) is not a fixed value but can vary based on vWF replenishment. The simulation results strongly point to the fact that the command signal generator or outer pressure control loop can be centered on increasing pulsatility while allowing a decrease in mean aortic pressure, or it can be centered on mean aortic pressure while allowing a decrease in pulsatility.

[0043] The duration of systole in humans at a normal heart rate HR ≒ 70 bpm (beats per minute) is usually approximately τ Systole (h) = 300 ms and varies slightly with heart rate. Patients in shock are typically characterized, among other things, by their heart rates reaching HR ≤ 120 bpm. Thus, the minimum duration of a cardiac cycle is assumed to be τ(h) = 500 ms. Furthermore, in patients with higher heart rates HR ≥ 120 bpm, the minimum duration of a cardiac cycle is approximately τ Systole A short systolic duration of (h)=250 ms is assumed.

[0044] Therefore, the given pulse duration τ of the rate pulse pulse (h) is expressed as τ pulse (h) = in the range of [200, ..., 300] ms, preferably τ pulse (h) = in the range [225,…,275] ms, most preferably around τ pulse It is recommended to set (h)=250ms.

[0045] Alternatively, a predetermined pulse duration τ of the velocity pulse pulse (h) is the systolic duration τ Systole It may be within the range of ±50% or ±100 ms for (h).

[0046] The pulse duration of the velocity pulse is adapted to the heart rate while taking into account the residual pulsatility in the artery of interest, and the period τ assist (h), preferably dependent on observations of previous heart rate and duration of preceding systole, may be obtained.

[0047] Additionally or alternatively, a speed reference signal n VAD setThe adjustment of (t) may be synchronized to the appearance of R waves in the patient's electrocardiogram (ECG) signal and / or may be set to a constant repetition rate, such as in the case of cardiac arrest.

[0048] According to one potential practical implementation, the VAD, e.g., in the form of a rotary blood pump, is equipped with an actuator, e.g., a rotary motor, which drives the blood pump to regulate the VAD-induced blood flow, Q. VAD (t) can be generated. Then, the speed command signal n VAD set (t) to the target speed level for the rotary motor, and the VAD speed n VAD By controlling (t), the VAD speed n VAD (t) can be changed. This allows the correction of pulsatility, i.e., the pulsatility difference ΔAoP pulse (h) is the speed reference signal n VAD set (t) with the corresponding adjustment, for example, the speed difference Δn VAD set (h), and the speed command signal n VAD set (t) is the base speed level n VAD set,basic From (h), the speed difference Δn VAD set (h) and the desired minimum pulsatility ΔAoP set by the controller. ~ (h) is generated. In this way, the controller is made to generate a higher corresponding speed command signal n VAD set (t)=n VAD set,basic (h) + Δn VAD set (h) to obtain the desired minimum pulsatility ΔAoP ~ It may be configured to achieve (h).

[0049] In general, the speed difference Δn VAD set (h) can also be made negative, for example to generate a negative velocity pulse.

[0050] Notably, the desired speed difference Δn VAD set (h) is the realized pulsatility difference ΔAoP pulse (h), which is generally a function of the amount of blood volume pumped into the arterial system in a given unit of time. It should be understood that any arterial blood pressure build-up is the end result of the volume of blood pumped into the arterial system in a unit of time with its inherent compliance and peripheral resistance.

[0051] Preferably, the control device further comprises a step of controlling the speed command signal n even outside the speed change interval. VAD set By adjusting (t), for example, the base speed level n VAD set,basic (h) is adjusted to obtain the desired mean arterial blood pressure (AoP) - (h) or to avoid any backflow through the pump into the ventricle, called regurgitant pump flow.

[0052] According to a further development, the control device, in particular the second closed-loop mechanism, is adapted to receive the speed command signal n both within and outside the speed change interval. VAD set Adjust (t) to obtain the desired minimum pulsatility ΔAoP ~ It can be configured to achieve (h).

[0053] According to a further development, the control device is additionally adapted to measure the beat-to-beat mean arterial blood pressure AoP - (h) is taken into account as a control constraint and the speed command signal n VAD set (t) can be configured to adjust.

[0054] For example, the control device may be VAD set By adjusting (t), a given threshold AoP - thr (h) Mean arterial blood pressure (AoP) - (h) may be configured to avoid the descent.

[0055] In addition, the control device is controlled by a speed command signal n VAD set By adjusting (t), it is possible to determine the time it takes for a specific characteristic event to occur within a specific period of time τ incr (h) the rate change interval (or rate pulse) may be configured to begin before the expected or predicted onset of a ventricular contraction of the assisted heart, i.e., a period τ from the expected or predicted onset of a corresponding characteristic event in the cardiac cycle. incr (h) Prior to triggering. This can be particularly important because there may be delays in the dynamic response of an individual VAD, e.g., a particular pump, due to the pump's inherent mechanical and / or fluid inertia and therefore the need for a waiting period before providing the desired effect.

[0056] For example, the onset of cardiac contraction, i.e., as defined by mitral valve closure time, may be detected based on the corresponding blood pressure signal, which may be the left ventricular pressure, for example, if the VAD is configured for left ventricular assistance.

[0057] For example, one may detect an atrial contraction preceding the ventricular contraction, and thus, if the onset of an atrial contraction is used as the event, the pump can be sped up, since this event occurs earlier than the systolic contraction event.

[0058] Alternatively or additionally, the predetermined event may be the occurrence of an R wave in an ECG signal of the assisted heart.

[0059] Period τ incr (h) can be useful in accounting for the fact that the velocity ramp of the VAD is slowed down by the fluid effect of the blood on the VAD drive. VAD set (t) should be increased according to a smooth trajectory, thereby avoiding hemolysis and other undesirable hemodynamic side effects, such as aspiration or VAD-induced cavitation, which may cause excessive acceleration of the blood.

[0060] In addition, the control device is configured to control a predetermined pulse duration τ pulse (h) followed by the reference signal n VAD set The pulse (t) may be configured to terminate.

[0061] Alternatively, the control device may be configured to control a heart rate dependent pulse duration τ assist (h), i.e. after a pulse duration adapted by the control device to the heart rate HR(h), the speed command signal n VAD set In particular, the controller may be configured to terminate the pulse of the rate command signal n(t) when at least one predetermined characteristic event of the cardiac cycle occurs. VAD set The pulse (t) may be configured to terminate.

[0062] In addition, the control device is configured to detect when at least one predetermined characteristic event of the cardiac cycle occurs or for a predetermined period of time τ red (h) Speed ​​reference signal n VAD set The pulse (t) may be configured to terminate.

[0063] For example, the predetermined characteristic event may be the onset of relaxation of the assisted heart and / or the closure of the aortic valve.

[0064] For example, the at least one event may be the onset of relaxation of the assisted heart. The controller may then be configured to derive the occurrence of the event based on a signal containing information about the characteristic event, e.g., the onset of relaxation. As a result, the rate command signal n VAD set The pulse at (t) can be synchronized, for example, with the occurrence of the maximum drop in intraventricular pressure of the assisted heart, which indicates the onset of ventricular relaxation (moment of relaxation) following the preceding systole.

[0065] Alternatively or additionally, the controller may be configured to derive the time of occurrence of at least one cardiac cycle event based on at least one internal signal of the controller, where an "internal signal" of the controller is used herein to mean a signal that is already internally available to the controller for analysis, such as a control signal provided by the controller to a VAD.

[0066] For example, the at least one internal signal may be a current provided to operate a VAD, e.g., a motor current provided to a VAD, and the controller may be configured to derive the occurrence time of at least one event per cardiac cycle based on analysis of the current signal and / or a processed version thereof, e.g., a time derivative, such as a first time derivative.

[0067] For example, the VAD may be a rotary blood pump as mentioned above. The blood pump may include an actuator, e.g., a rotary electric motor, which drives a rotary propulsion element, e.g., an impeller, to generate the appropriate blood flow. During operation of the blood pump, the motor current consumption by the motor controls the individual target speed levels of the motor and rotary propulsion element in response to a preset speed command signal n VAD set The motor current required to achieve the target speed I VAD (t) is the current pressure difference Δp(t) that the blood pump must overcome, e.g., the difference between the aortic pressure AoP(t) and the left ventricular pressure LVP(t). Δp(t)=AoP(t)-LVP(t) It depends on.

[0068] In other words, the current delivered to a blood pump corresponds directly to the current required by the blood pump's motor to achieve a set speed. I VAD (t) = f(n VAD set (t),Δp(t) It becomes.

[0069] Thus, the motor current supplied to the VAD by a controller, or supplied by a power supply unit controlled by the controller, may be used as an internal signal to derive the occurrence of at least one event per cardiac cycle.

[0070] The controller is further adapted to calculate the current VAD induced blood flow, Q, based on the current signal and based on known calculation specifications involving pump characteristic relationships between motor current, pump flow and pressure difference at a given speed. VAD The method may be configured to estimate (t).

[0071] Alternatively or additionally, the control device may be configured to derive the occurrence time of at least one cardiac cycle event from at least one external signal provided to the control device. By "external signal" it is meant herein signals received by the control device from external sensors of the VAD, such as one or more blood pressure sensors, and / or from external devices, such as a patient monitoring unit or an electrocardiograph (ECG). Such external signals may be fed into the control device via a corresponding interface or input terminal, making them available to the control device for processing and / or analysis by the control device.

[0072] For example, the measurement signal may represent at least one of the following, to give only a few examples: the pressure difference Δp(t) between the outlet of a VAD and its inlet, the intraventricular pressure LVP(t) of the assisted heart, the aortic pressure AoP(t) adjacent the assisted heart, the vena cava pressure CVP(t) adjacent the assisted heart, and the pulmonary artery pressure PAP(t) adjacent the assisted heart. Any of these measurement signals will include information in the waveform describing the occurrence of particular cardiac cycle events.

[0073] For example, if the VAD is a rotary blood pump as discussed above, it may have an inlet for drawing blood from the heart, e.g., from within the ventricles, and an outlet for ejecting blood into a blood vessel adjacent to the heart, such as the artery of interest, which may be the aorta or pulmonary artery depending on whether the VAD is inserted into the left or right side of the heart.

[0074] For example, as disclosed in Patent Document 1, the VAD may be equipped with at least one of a pressure sensor that measures the blood pressure at the inlet of the VAD itself, such as the ventricular pressure in the assisted heart, and a pressure sensor that measures the blood pressure in a blood vessel adjacent to the heart, such as the blood pressure in the aorta or pulmonary artery adjacent to the assisted heart. Alternatively or in addition to this, the VAD may be equipped with a differential pressure sensor that measures the difference in blood pressure between the outlet and inlet of the VAD itself.

[0075] Additionally, the controller may be configured to receive, store and analyze at least one measurement signal containing information about a feature of a cardiac cycle, from which a current operating phase of the heart in that cardiac cycle can be estimated, and the controller may be configured to predict the occurrence of the particular feature in a next cardiac cycle based on information about a previous cardiac cycle.

[0076] Basically, in any embodiment, the at least one measurement signal may be at least one of an ECG signal, a measurement signal representative of the blood pressure in the left or right ventricle of the heart, a measurement signal of the blood pressure in a vena cava adjacent to the heart or in the aorta, or a measurement signal of the blood pressure in the pulmonary artery.

[0077] That is, to predict the next occurrence of at least one event based on information about the preceding cardiac cycle, the selected signal preferably includes information about the cardiac cycle, such that the occurrence of at least one cardiac cycle event is predicted based on the selected measurement signal and on events detected in the preceding cardiac cycle.

[0078] Additionally or alternatively, the controller may be configured to remove from the measurement signals the effects of active cardiac assistance by the VAD, and in particular, the controller may be configured to analyze at least two, preferably independent, measurement signals by data fusion with a view to detecting a predefined intracardiac event independent of VAD-induced pressure changes on the dynamic behavior of the heart.

[0079] According to a specific embodiment, the control device is configured to set the VAD speed so that the amount of blood ejected by the VAD into the artery of interest, e.g., the aorta or pulmonary artery, during the diastole of the assisted heart's cardiac cycle is sufficiently small to preserve blood volume in the corresponding ventricle and to provide a suitable minimum peak blood flow through co-ejection of the VAD and ventricle during systole, i.e., a minimum peak blood flow of preferably about 6 L / min, more preferably 7 L / min, and most preferably 8 L / min or greater (as discussed above).

[0080] The systolic peak flow will depend largely on the natural cardiac co-ejection function, which in turn depends on the ventricular preload, ventricular filling level, and cardiac contractility level, as well as the achievable peak flow of the VAD. total | max (h) and total beat-to-beat ejection volume EV(h) should provide an adequate increase in systolic systemic blood pressure as described above. However, this also depends on the patient's body mass index or body surface area, vascular compliance, and peripheral resistance. In other words, in small patients, Q total | max A minimum total peak flow of (h)=6 L / min may be sufficient, although larger patients (as discussed above) may require more total peak flow, especially when the vascular bed is relaxed or widely open.

[0081] In addition, the control device may be configured to adjust the resulting beat-to-beat mean arterial blood pressure AoP - (h) is a given threshold AoP - thr(h) If the speed reference signal n in pulse form is not lower than VAD set (t) may be configured to be adjusted within the cardiac cycle.

[0082] Minimum VAD-induced blood flow Q VAD (h) may be associated with the minimum cardiac assistance to be provided by the VAD to the failing heart. The idea is to operate the VAD in such a way that the desired vWF replenishment is obtained and the minimum required blood flow supply is ensured. For example, the current required blood flow may be related to the current perfusion demand of the patient, taking into account periods of high assistance, e.g., daytime activity, walking, stair climbing, etc., and the VAD may operate at a relatively high average speed during those periods. Periods when the patient has a low perfusion demand, e.g., at rest, while sleeping, etc., may be used to operate the VAD at a lower average speed. This may help to increase pulsatility and aid in the replenishment of vWF while maintaining a certain degree of blood flow support. Of course, the specific VAD-induced blood flow Q VAD Advanced schemes are also possible in which the current cardiac assistance demand corresponding to (h) is taken into account in a continuous manner. Thus, the controller may be configured to use any available surplus between the current required minimum blood flow and the maximum blood flow that can be provided by the VAD to restore and maintain residual pulsatility as proposed herein.

[0083] It would be more sensible to synchronize the rate change in a "y in x" fashion, i.e. to generate the rate pulses of the present invention only in y of x consecutive cardiac cycles. For example, the rate pulses aimed at restoring or maintaining the desired minimum pulsatility could be induced in a 1 in 2, 1 in 3 or 1 in 4 fashion, or in a 2 in 3, 2 in 4 or 2 in 5 fashion, i.e., in one of every 2, 3 or 4 consecutive cardiac cycles, or in two of every 3, 4 or 5 consecutive cardiac cycles, respectively. This would be particularly useful when the heart rate is too high or the level of pump assistance to the heart is inadequate, in which case pulsatility support is provided only intermittently. As it turns out, this can be successfully used for the purpose of vWF replenishment. For example, the control device could be configured to change the VAD rotation speed n in at least y of the other xy consecutive assisted cardiac cycles. VAD (t), and thus to keep the beat-to-beat mean arterial pressure (AoP) above a given threshold. - (h) ≧ AoP - thr (h)) may be additionally configured.

[0084] The above-discussed functions or functionalities of the control device can then be realized by a corresponding information processing unit in the form of hardware, software or any combination thereof, which can be implemented by a corresponding computer program having a software code that causes the information processing unit to execute the respective required control steps. Such programmable information processing units are well known in the art and to those skilled in the art, and therefore need not be described in detail here. Furthermore, the information processing unit may also include specific dedicated hardware serving specific functions, such as one or more signal processors for processing and / or analyzing the measurement signals discussed above. Furthermore, a separate unit for controlling the speed of the drive of the VAD may also be implemented by a separate software module.

[0085] The corresponding computer program can be stored on a data carrier and incorporated therein, or alternatively, the computer program can be transferred in the form of a data stream which also contains the computer program, for example via the Internet, making a data carrier unnecessary.

[0086] In a second aspect of the invention there is provided a VAD comprising one of the control devices according to the first aspect of the invention. For example the VAD may be a rotary blood pump, i.e. a blood pump driven by a rotary motor.

[0087] For example, such a blood pump may be of the catheter type and implanted or placed directly within the heart via the corresponding blood vessels.

[0088] For example, the VAD may be a blood pump such as that disclosed in US Pat. No. 6,399,633, and may be specialized for temporary placement or implantation within the left or right heart of a patient.

[0089] Preferably, the VAD is a low inertia device having one or more of the following characteristics, but not limited to: (1) the moving parts of the VAD, especially the rotating parts, e.g., rotor or impeller, can be made of lightweight materials, e.g., plastics, composites, etc., to have a low mass, (2) the drive means, e.g., electric motor, can be located near, preferably in close proximity to, and most preferably adjacent to, the part driven by the motor, e.g., rotor or impeller, and, in the case of a catheter, should preferably not have any rotary drive cables or drive wires other than electrical wiring, (3) the coupling or connection means, e.g., shaft, of the motor to the part driven by the motor, e.g., rotor or impeller, can be short, and (4) all moving parts, especially the rotating parts, of the VAD can be small in diameter. Note that the above list of characteristics is not claimed to be exhaustive, and the device may have other or alternative characteristics that may make it a low inertia device.

[0090] The invention will now be described, by way of example only, with reference to the accompanying drawings in which: [Brief description of the drawings]

[0091] [Figure 1] FIG. 1 illustrates an embodiment of a VAD positioned within the aorta and extending through the aortic valve into the left ventricle of the heart, and a block diagram of an embodiment of a control device for the VAD. [Diagram 2] FIG. 2 illustrates an aspect of the example VAD of FIG. 1 in greater detail. [Diagram 3] FIG. 3 illustrates the principles of pulsatile rate control to restore and / or maintain blood pulsatility by the VAD of FIGS. 1 and 2 under the control of the controller of FIG. 1 by showing example signal waveforms representing a) aortic pressure (AoP(t)), b) left ventricular pressure (LVP(t)), c) ECG (ECG(t)) and d) rate command signal trajectory (nVAD set(t)), and e) corresponding trigger signal sequence (σ(t)). [Figure 4] FIG. 1 shows an electrical equivalent circuit of an electrical model that approximates the so-called intra-aortic Windkessel effect. [Diagram 5] FIG. 1 shows the results of five different simulation scenarios for the heart blood flow Qheart(t) and pump blood flow Qpump(t) (top panel) and the aortic pressure AoP(t) (bottom panel). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0092] A catheter-based rotary blood pump (hereafter referred to as the "blood pump") described herein as one exemplary embodiment of a VAD is shown on the left hand side of Figure 1. This exemplary blood pump is shown in more detail in Figure 2.

[0093] As noted above, one of the important physical requirements found by the inventors to be met in a VAD for use in the proposed application is the absence of any significant inertia. Rotary blood pumps, such as the catheter-type blood pump shown in Figure 2, do not have any significant inertia that would interfere with the implementation of the proposed intra-pulse velocity modulation speed control scenario.

[0094] This blood pump is based on a catheter 10, which is inserted into the left ventricle 16 of the heart via the aorta 12 and the aortic valve 15 (catheter-type blood pump). As shown in detail in FIG. 2, in addition to the catheter 10, the blood pump includes a rotary pumping device 50 fastened to the end of the catheter tube 20. The rotary pumping device 50 includes a motor section 51 and a pump section 52 located at a certain axial distance from the motor section 51. A flow cannula 53 is connected to the pump section 52 at one end and extends from the pump section 52, and an inflow cage 54 is located at the other end. A soft and flexible tip (end) 55 is attached to the inflow cage 54. The pump section 52 includes a pump housing with an outlet opening 56. The pumping device 50 further includes a drive shaft 57 protruding from the motor section 51 into the pump housing of the pump section 52. The drive shaft 57 drives an impeller 58 as a propulsion element, so that blood can be drawn in through the inflow cage 54 and expelled through the outlet opening 56 during operation of the blood pump.

[0095] If appropriately adapted, pumping in the reverse direction is also possible with the pumping device 50, as may be desired, for example, when placing the blood pump in the right heart. For completeness in this regard, the rotary blood pump shown in FIG. 1 is an example of a VAD, which is placed in the left heart and used for left heart assist. For right heart assist, the rotary blood pump of this example may be placed in the right heart, with optional introduction into the right heart from the vena cava, so that blood may be ejected into the pulmonary artery. The blood pump in this arrangement may be configured to draw blood from the vena cava or the right ventricle and eject it into the pulmonary artery. Thus, the principles and functionality described according to one embodiment may be correspondingly replicated for right heart assist. A detailed description is therefore not necessary.

[0096] 1 and 2, three wires, two signal wires 28A and 28B and a power supply wire 29 for supplying current to the motor section 51, pass through the catheter tube 20 of the catheter 10 and lead to the pumping device 50. The proximal ends of the two signal wires 28A, 28B and the power supply wire 29 are connected to the control device 100. Of course, additional wires may be provided for other functions, for example a purge fluid line may also pass through the catheter tube 20 of the catheter 10 and lead to the pumping device 50. Additional wires may be added based on other sensing technologies.

[0097] As shown in FIG. 2, the signal lines 28A, 28B are components of a blood pressure sensor, each having a corresponding sensor head 30, 60, which is arranged externally on the housing of the pump part 52. The sensor head 60 of the first pressure sensor is associated with the signal line 28B. The signal line 28A is associated and connected with the sensor head 30 of the second blood pressure sensor. An example of such a blood pressure sensor is an optical pressure sensor that functions according to the Fabry-Perot principle, as described in US Pat. No. 5,399,363, in which case the two signal lines 28A, 28B are optical fibers. However, other pressure sensors may be used instead. In principle, the signals of the pressure sensors, i.e. signals carrying specific information about the pressure at the location of the sensors, may come from any suitable physical source, for example optical, fluid or electrical sources, etc., and are transmitted via the respective signal lines 28A, 28B to the corresponding inputs of the data processing unit 110 of the control device 100. In the example shown in FIG. 1, the pressure sensors are arranged so that the sensor head 60 measures the aortic pressure AoP(t) and the sensor head 30 measures the left ventricular pressure LVP(t).

[0098] The data processing unit 110 is configured for the purposes of capturing all external and internal signals, performing actual signal processing including calculation of the difference between two pressure signals as the basis for pump flow estimation, signal analysis for detecting characteristic events within the cardiac cycle based on the captured and calculated signals, and generating a trigger signal sequence σ(t) for triggering the speed command signal generator 120 by a trigger signal generator (see below for details).

[0099] The data processing unit 110 is connected via corresponding signal lines to further measurement devices 300, such as a patient monitoring unit 310 and an electrocardiograph 320, which are just two examples, and which may generate and thus use useful signals in other measurement devices. The electrocardiograph 320 supplies an ECG signal ECG(t) to the data processing unit 110.

[0100] The controller 100 further comprises a user interface 200, which includes a display 210 and a communication interface 220. The display 210 displays configuration parameters, parameter monitoring results, e.g., pressure signal measurements, and other information. Additionally, the communication interface 220 allows a user of the controller 100 to interact with the controller 100, e.g., to change system-wide configurations.

[0101] The data processing unit 110 is configured, inter alia, to derive or predict the occurrence of one or more predetermined characteristic events in the cardiac cycle of the assisted heart by real-time analysis of the current signal values ​​and to use them in generating a trigger signal sequence σ(t) by the trigger signal generator 120. The obtained trigger signal sequence σ(t) is sent to the rate command signal generator 120 for triggering a change in the rate command signal.

[0102] Furthermore, the data processing unit 110 processes these speed command signals n VAD set (t) in the cardiac cycle. That is, the data processing unit 110 is also configured to predict the time of occurrence of at least one predetermined characteristic event in a future cardiac cycle based on stored information about characteristic events occurring in the current and / or previous cardiac cycles.

[0103] One particular characteristic event of the cardiac cycle may be the onset of cardiac contraction at the onset of systole. The occurrence of such a characteristic event may be detected or predicted, and the speed command signal n VAD set It is used as an event to synchronize the (t) pulse with the cardiac cycle.

[0104] The speed command signal generator 120 generates a speed command signal n VAD set (t) and supplies it to a speed control unit 130 in the form of an event-based command signal generator, a feedforward mechanism (first mechanism) or an outer feedback closed loop mechanism for pressure control (second mechanism).

[0105] In the first mechanism, at least one sequence of trigger signals σ(t) is provided by the data processing unit 110, which triggers the speed command signal generator 120. In the second mechanism, the data processing unit 110 provides external and internal signals to a pressure control algorithm (command signal generator 120) operating in the form of an outer feedback loop, and the pressure control algorithm is triggered by at least one sequence of trigger signals σ(t) provided by the data processing unit 110, thereby generating a speed command signal n VAD set (t) to generate the desired minimum pulsatility ΔAoP ~ Achieve (h).

[0106] In response to this, the speed control unit 130 supplies a motor current I to the motor section 51 of the pumping device 50 via the power supply line 29 led into the catheter tube 20. VAD (t) to obtain the speed reference signal n VAD set (t) according to the VAD speed n VAD (t) is controlled by the supplied motor current I VAD The current level of (t) is the speed reference signal n VAD set t corresponds to the current currently required by the pumping device 50 to establish the target speed level as determined by (t). Via power supply 29 the pump also communicates with the control unit 100.

[0107] Measurement signal, e.g. the supplied motor current I VAD (t) is used as a signal representative of the internal signals of the control device 100 and is provided to the data processing unit 110 for further processing.

[0108] A control device 100 according to a first aspect of the invention is configured to vary the speed of a blood pump of one embodiment of a cardiac assist VAD, FIGS. 1 and 2.

[0109] The control device 100 is configured, inter alia, to change the speed of the blood pump 50 during the cardiac cycle of the assisted heart to change the blood flow therein, and to synchronize the speed change with the heartbeat by at least one event per cardiac cycle related to a predetermined event during the cardiac cycle. That is, to provide at least one sequence of trigger signals σ(t) by the trigger signal generator of the data processing unit 110 to trigger the speed command signal generator 120, the data processing unit may obtain information about at least one specific event during the cardiac cycle, detect the occurrence of the event, and set the trigger signal sequence σ(t) using the signal information corresponding thereto.

[0110] However, the trigger signal generator providing the trigger signal sequence σ(t) may be based on a number of cardiac cycle events that are detected during each cardiac cycle and analyzed to derive a corresponding trigger signal sequence σ(t) thereby generating a command signal n VAD set (t) to adjust the speed of the blood pump 50 VAD Note that (t) may be changed.

[0111] As discussed above, the blood pump includes a rotary pumping device 50 having an impeller speed n VAD (t) is controlled by the speed control unit 130. The blood pump speed command signal n VAD set (t) is regulated by command signal generator 120.

[0112] According to the first embodiment of the proposed blood flow change by a blood pump, the control device 100, in particular its speed command signal generator 120, generates a speed command signal n VAD set (t) and the resulting VAD speed n VAD By changing (t), the VAD-induced blood flow Q VAD (t) to induce a pressure pulse during each cardiac cycle.

[0113] For better understanding, an example of the potential effect of speed changes is shown in Figure 3, which is accompanied by example waveforms.

[0114] The waveform in Figure 3a) represents the aortic pressure signal, which shows the physiological (unassisted) aortic pressure AoP(t) (dashed line) and the desired (assisted) aortic pressure AoP ~ There is a difference between (t) (solid line).

[0115] The waveform in FIG. 3b) represents a signal related to the left ventricular pressure LVP(t) together with examples of characteristic pressure values ​​and / or cardiac cycle events that may be used to generate or derive the trigger signal sequence σ(t).

[0116] The waveform in Figure 3c) represents an ECG signal.

[0117] The diagram in FIG. 3 illustrates, by way of example, the principle of pulsatile blood pressure restoration and maintenance using the blood pump of FIGS. 1 and 2 under the control of the control device 100 in FIG.

[0118] For this purpose, Fig. 3d) shows the speed reference signal n VAD set One concrete example of (t) is shown.

[0119] In Fig. 3e) the corresponding trigger signal sequence σ(t) is plotted.

[0120] Speed ​​command signal n VAD set The signal n(t) is used to vary the pump speed and corresponds to the signal output of the speed command signal generator 120 and is sent to the speed control unit 130. The generation of the event-based speed command signal based on the trigger signal sequence σ(t), i.e., the event-based closed-loop pressure control, results in the modified speed command signal n VAD set (t) occurs and the change is synchronized with the heartbeat.

[0121] command signal n VAD set (t) is the base speed level n VAD set (t)=n VAD set,basic (j) from the boosted speed level at the start of the speed pulse n VAD set (t)=n VAD set,basic (j) +Δn VAD set (j) The velocity increases to Δn VAD set (j) represents the speed difference within the speed pulse.

[0122] In Figure 3, the start of the rate pulse is synchronized with the end of diastole. Furthermore, at the end of the rate pulse, the rate is increased to the augmented rate level. n VAD set (t)=n VAD set,basic (j) +Δn VAD set (j) From the base speed level n VAD set (t)=n VAD set,basic (j) It has also been shown that the level of β-amyloid in the blood decreases and then returns to normal.

[0123] In Figure 3, the end of the rate pulse is synchronized with the end of systole. Each of these rate changes represents a potential implementation of rate changes to achieve a desired minimum pulsatility, as discussed in the Summary section of this application.

[0124] The speed reduction is performed by increasing the speed reference signal n VAD set The pulse of (t) has a heart rate dependent pulse duration τ assist The command signal generator 120 is configured to generate a rate pulse having a heart rate dependent pulse duration, the rate pulse being triggered to terminate after heart rate HR(h), i.e., its pulse duration is adapted to the heart rate HR(h).

[0125] Alternatively, the rate reduction may be performed for a given pulse duration τ pulse To achieve this, the command signal generator 120 may be triggered to generate a pulse of a predetermined duration τ pulse It is sufficient to configure the device to generate a velocity pulse exhibiting (j).

[0126] In the illustrated example (FIG. 3d), the speed difference Δn VAD set The speed increase of (j) minutes occurs at time t in this example. LVP j,ED The speed drop at the end of the speed pulse is at time t AoP j,ES It ended at.

[0127] Preferably, during operation, the speed command signal generator 120 is controlled to generate a speed difference Δn VAD set The present invention is configured to control the pulsatility ΔAoP(h) by adjusting ΔAoP(h) accordingly. As discussed above, to ensure that vWF deficiency cannot occur and / or that microvascular perfusion can be improved, a desired minimum pulsatility is set to ΔAoP(h). ~ It is considered sufficient to keep the range of (h) = [15, ..., 30] mmHg.

[0128] Additionally, as discussed above, the data processing unit 110 may also calculate the current beat-to-beat mean arterial blood pressure AoP - (h) and providing its current value to the speed reference signal generator 120. With this in mind, the speed reference signal generator 120 is further configured to VAD set (t) is adjusted to preferably avoid a drop in arterial blood pressure below a certain threshold and to control the AoP - (h) ≧ AoP - thr (h).

[0129] As discussed in the Summary section, sufficient minimum blood pressure pulsatility may be restored and / or maintained by adjusting the speed of the rotary pumping device 50, thereby increasing the VAD-induced blood flow QVAD (t) during the diastole of the cardiac cycle and / or substantially increasing it during the systole of the cardiac cycle. VAD set By adjusting (t), the volume of blood ejected into the aorta (or pulmonary artery) during the diastole of the assisted heart's cardiac cycle is reduced to leave a predetermined volume in the left (right) ventricle, and an appropriate blood volume is co-ejected during systole by the left (right) ventricle and the rotary pumping device 50. In other words, the reduction in intradiastolic velocity also allows the heart to fill appropriately, thereby enabling the rotary pumping device 50 and the natural heart to co-eject blood during systole. In this regard, the inventor has found that the pump and the natural heart can co-eject blood during systole. Q total | max (h)=Q heart | max (h)+Q pump | max (h)>6L / min,…,10L / min This induces a total peak flow of EV(h) = EV heart (h)+EV pump (h)=40,…,70ml The total ejection volume should be such that the desired minimum pulsatility ΔAoP ~ (h) ≥ 15, ..., 30 mmHg can be achieved. However, the desired minimum pulsatility ΔAoP ~ (h) is not a fixed value, but can vary with vWF replenishment. Furthermore, if the natural pulsatility of the weak heart alone is above the desired minimum pulsatility, there would of course be no need to reduce that pulsatility.

[0130] The inventors have determined that the pump's beat-to-beat peak flow, Q pump | max (h) and that of the heart Q heart | max (h) and the corresponding pump total ejection volume per beat, EV pump (h) and that of the heartheart (h) was confirmed by a mathematical model that constitutes an electrical equivalent circuit. The model used is depicted in Figure 4.

[0131] Figure 4 shows the circuit of an electrical model that approximates the dynamics of the so-called intra-aortic Windkessel effect when blood is ejected by the heart. The electrical model consists of a resistor (R1 = 0.05 Ω) representing the resistance of the aortic valve, another resistor (R2 = 1.32 Ω) in series with it representing the resistance of the peripheral arterial system, and a capacitor (C2 = 1.7 F) representing the arterial compliance. Furthermore, the model calculates the (residual) cardiac output Q heart (h) and the blood flow of the pump Q pump (h) is considered as the current source. A standard pump, Impella® 5.0, was used to represent a rotary blood pump; see Non-Patent Document 2 for further details.

[0132] Figure 5 shows the results of five different simulation scenarios. The table below shows the results of the five simulation scenarios in terms of total blood flow (Q total ΔAoP(j)) along with additional information on the corresponding pulsatility (ΔAoP(j)).

[0133] In Figure 5, the scenarios (1) to (5) considered from left to right are as follows:

[0134] Scenario (1) - "Healthy Heart": This assumes the natural function of the heart. heart | max A cardiac peak flow of (j) = 15 L / min and a pulsatility of ΔAoP(j) = 40 mmHg (120 / 80 mmHg) are typical mean aortic blood pressures (AoPs). - (j)=105.4mmHg.

[0135] Scenario (2) - "Weak heart, no support": The heart function is reduced to 1 / 3 of its original function. heart | maxA peak cardiac flow of ΔAoP(j)=5.4 L / min and a very low pulsatility of ΔAoP(j)=14.5 mmHg (42 / 28 mmHg) were observed without the pump implanted. - (j) was obtained together with an unphysiologically low mean aortic blood pressure of 36.8 mmHg.

[0136] Scenario (3) - "Full unloading (P4)": The aim is to generate maximum flow, and the failing heart is assisted by the pump at speed level P4. total | max (j)=Q heart | max (j)+Q pump | max The total peak flow of (j) = 8.5 L / min and the moderate pulsatility of ΔAoP(j) = 17.2 mmHg (96 / 79 mmHg) are the AoP values. - This occurs with a physiological mean aortic blood pressure of (j) = 89.8 mmHg.

[0137] Scenario (4) - "Low pulsatility (P4 / P2)": A weak heart is assisted by a pump, the speed of which is changed to the same speed as in scenario (3) (P4) during systole and a lower speed (P2) during diastole. total | max (j)=Q heart | max (j)+Q pump | max The total peak flow of (j) = 8.5 L / min and the moderate pulsatility of ΔAoP(j) = 20.4 mmHg (78 / 58 mmHg), which is higher than that of scenario (3), are the main reasons for the AoP. - (j) was obtained at a low mean aortic pressure of 70.6 mmHg.

[0138] Scenario (5) - "High pulsatility (P9 / P2)": A weak heart is assisted by a pump that changes its speed to the highest possible speed during systole (P9) and a lower speed during diastole (P2). total | max (j)=Q heart | max (j)+Q pump | maxA strong total peak flow of (j) = 10.3 L / min and the highest possible pulsatility of ΔAoP(j) = 27.4 mmHg (95 / 69 mmHg) are the AoP - (j) was obtained at a moderate mean aortic pressure of 85.2 mmHg.

[0139] It should be noted that scenarios (3)-(5) assume that the heart ejects the same amount during systole regardless of the degree of diastolic unloading by the pump. [Table 1]

[0140] Overall, these simulation results highlight the fact that the rate change can be focused on increasing pulsatility while accepting a decrease in mean aortic pressure, or on increasing mean aortic pressure while accepting a decrease in pulsatility, taking into account physical and physiological constraints such as very low inertia and hemolysis.

[0141] In particular, the data processing unit 110 triggers the rate command signal generator 120 to generate a rate command signal n at a detected or predicted occurrence time of at least one predetermined event in the cardiac cycle. VAD set At least one sequence of trigger signals σ(t) generated by a trigger signal generator of the data processing unit 110 is provided to the speed reference signal generator 120.

[0142] In a preferred embodiment, as illustrated in FIG. 3, a speed reference signal generator 120 generates a speed reference signal n VAD set The increase in (t) is determined by a predetermined period τ from the occurrence of a characteristic event of the cardiac cycle, i.e., an event that generates the trigger signal sequence σ(t). incr(h) before the start of the trigger signal sequence σ(t). This trigger signal sequence σ(t) can be used to change the pump speed in a moderate manner to avoid aspiration, blood damage, etc., or to allow for a timely increase in pump speed to account for the phase difference between the speed change associated with systolic co-ejection and the resulting pressure change (vasculature compliance and blood inertia).

[0143] In the example depicted in Fig. 3, the onset of left ventricular contraction is used as the characteristic time, and the trigger signal sequence σ(t) is generated by the trigger signal generator taking this into account. The left ventricular contraction starts immediately after the occurrence of an R-wave in the corresponding ECG signal. The speed command signal generator 120 may therefore be configured to derive the trigger signal sequence σ(t) on the basis of an ECG signal provided to the data processing unit 110. The data processing unit 110 may be configured to receive an ECG signal from an (external) ECG device 320 and to generate the trigger signal sequence σ(t) by means of the trigger signal generator.

[0144] As mentioned above, other measurement signals, which indicate events whose occurrence precedes the beginning of the intrasystolic ejection period, such as the beginning of the left atrial contraction, and which can be used as events, may also be used by the data processing unit 110 to generate the trigger signal sequence σ(t). For example, in FIG. 3b), some characteristic values ​​and characteristic times are shown as examples for the signal related to the left ventricular pressure LVP(t), namely its minimum value LVP min (j), the highest LVP min (j), maximum time-course change dLVP(j) / dt | max and the minimum time-course change dLVP(j) / dt| min is marked.

[0145] In general, the speed reference signal generator 120 generates speed reference signals n by at least one sequence of trigger signals σ(t) provided by the data processing unit 110. VAD set Adjustment of (t) is synchronized with the cardiac cycle to cause the velocity pulse to begin prior to the onset of ventricular contraction and / or the occurrence of an R wave in the ECG signal.

[0146] Speed ​​command signal n VAD set The predetermined period τ for the start of the rise of (t) incr (h) is, for example, a time interval of approximately τ from the associated characteristic events in the cardiac cycle. incr (h)=150 ms, preferably τ incr (h)=100 ms, most preferably τ incr (h)≦100 ms in advance. incr (h) is believed to prevent the blood from being accelerated too quickly, reducing the likelihood of blood damage and / or unwanted hemodynamic effects. VAD set (t) to adjust the VAD speed n VAD (t) is configured to vary smoothly.

[0147] As a concrete example, Figure 3d) shows the VAD speed n VAD (t) is a linearly increasing and decreasing speed reference signal n VAD set Although (t) is shown, other forms are possible, such as an exponential ramp-up or ramp-down.

[0148] The speed command signal generator 120 then generates the predetermined pulse duration τ pulse After (h), the VAD speed n VAD Adjust (t) to the original speed level n VAD set,basic It is configured to terminate the current speed pulse by returning to (t).

[0149] Alternatively or additionally, the rate command signal generator 120 may be configured to generate a rate command signal n VAD set (t) to adjust the VAD speed n VAD It may be configured to change (t) to terminate the current speed pulse.

[0150] In a preferred embodiment, the predetermined event is the onset of relaxation of the assisted heart and / or the closure of the aortic valve. In this case, the rate command signal n is generated before, during or after the predetermined cardiac cycle characteristic event. VAD set A predetermined period τ for starting the reduction of (t) red (h) may also be taken into consideration. Preferably, the trigger for terminating the velocity pulse is part of the trigger signal sequence σ(t) and occurs a period τ after ventricular relaxation begins. red (h) prior to the trigger signal being provided by data processing unit 110. Preferably, the trigger signal is based on a prediction of the onset of ventricular relaxation detected during the preceding cardiac cycle.

[0151] For example, closure of the aortic valve can be determined when the left ventricular pressure LVP(t) drops below the aortic pressure AoP(t) or, equivalently, when the pressure difference between the inlet 54 and outlet 56 of the flow cannula 53 drops below zero.

[0152] The data processing unit 110 is further adapted to derive a trigger signal sequence σ(t) from at least one signal containing information relating to a characteristic event within a cardiac cycle, the assisted cardiac aortic valve closure.

[0153] For example, useful signals would be measured signals representing the left ventricular pressure LVP(t) of the assisted heart and / or the aortic pressure AoP(t) adjacent the assisted heart, or, if the blood pump is configured for assisting and placement on the right side of the heart, signals representing the blood pressure in the vena cava CVP(t) adjacent the assisted heart and / or the right ventricular pressure RVP(t) and / or the pulmonary artery pressure PAP(t) adjacent the assisted heart.

[0154] The data processing unit 110 calculates the required motor current I supplied to the rotary pumping device 50 by the speed control unit 130. VAD As discussed elsewhere in this application, the required motor current I VAD(t) reflects the energy required by the rotary pumping device 50 to follow the set speed value. Thus, the command signal generator 120 may be triggered by a corresponding series of trigger signals σ(t) provided by the data processing unit 110.

[0155] Preferably, the data processing unit 110 is configured to receive, store and analyze at least one measurement signal containing characteristic information of the circulatory system and the cardiac cycle, and to predict at least one beat-to-beat event based on the analysis of the previous cardiac cycle. Most preferably, the data processing unit 110 is configured to filter the effects of pump-induced pressure changes by analyzing at least two measurement signals, and to reliably detect characteristic events in the cardiac cycle.

Claims

1. The rotation speed (n ＶＡＤ The control device (100) controls the rotation speed (n ＶＡＤ (t)) and by at least one sequence of trigger signals (σ(t)) related to at least one predetermined characteristic event within the cardiac cycle. ＶＡＤ A control device configured to synchronize the modification of the time course (t) with the heart rate.

2. The control device (100) of claim 1, wherein the rotational speed (n ＶＡＤ (t)) for a given pulse duration (τ ｐｕｌｓｅ (h)) or heart rate dependent pulse duration (τ ａｓｓｉｓｔ (h)) to obtain a predetermined desired minimum pulsatility (ΔAoP ～ (h)) in the artery of interest within said cardiac cycle, and synchronising the initiation and / or termination of said rate modification with said at least one sequence of trigger signals (σ(t)).

3. The control device (100) of claim 2, further comprising a speed command signal (n ＶＡＤ ｓｅｔ (t)) and the rotation speed (n ＶＡＤ (t)) to change the predetermined desired minimum pulsatility (ΔAoP ～ (h)) and The first mechanism is an open-loop control mechanism, and the speed command signal (n ＶＡＤ ｓｅｔ (t) is varied between predetermined rotational speed levels using a command signal generator (120); or The second mechanism is a closed loop pressure control in a feedback system, and the speed command signal (n ＶＡＤ ｓｅｔ (t) is automatically set for each heartbeat (h); A control device configured to achieve the above.

4. The control device (100) of claim 3, wherein the speed command signal (n ＶＡＤ ｓｅｔ (t)) to obtain the predetermined desired minimum pulsatility (ΔAoP ～ (h)) a control device configured to achieve this via the second mechanism.

5. A control device (100) according to any one of claims 2 to 4, comprising: ＶＡＤ (t)) to achieve the predetermined desired minimum pulsatility (ΔAoP ～ (h)) in only y of x consecutive assisted cardiac cycles, where x is an integer greater than 2 and y is an integer such that y≦x.

6. A control device (100) according to claim 5, further comprising: a control unit for controlling the rotation speed (n) of the VAD (50) in at least y consecutive other x-y consecutive assisted cardiac cycles. ＶＡＤ (t)), the beat-to-beat mean arterial blood pressure (AoP － (h)) to a predetermined threshold value (AoP － ｔｈｒ (h) above the control device.

7. The control device (100) according to any one of claims 2 to 6, further comprising: ＶＡＤ ｓｅｔ (t)) to obtain beat-to-beat mean arterial blood pressure (AoP － (h)) to a predetermined threshold value (AoP － ｔｈｒ (h) a control device configured to keep the

8. The control device (100) according to any one of claims 2 to 7, characterized in that the control device (100) is arranged to detect a first predetermined period (τ) from the occurrence of one of the at least one predetermined characteristic event. ｉｎｃｒ (h)) before the speed command signal (n ＶＡＤ ｓｅｔ(t)), the characteristic event being preferably at least one of the onset of ventricular contraction and the occurrence of an R wave (R) in an electrocardiogram or ECG signal provided from a patient with an assisted heart.

9. The control device (100) according to any one of claims 2 to 8, wherein the predetermined pulse duration (τ ｐｕｌｓｅ (h))) and the adapted heart rate dependent pulse duration (τ ａｓｓｉｓｔ (h)), the occurrence of one of the at least one predetermined characteristic event in the cardiac cycle, a second predetermined period (τ ｒｅｄ (h)) ＶＡＤ ｓｅｔ (t)), wherein the at least one predetermined characteristic event in the cardiac cycle is preferably at least one of an onset of ventricular relaxation of the assisted heart and aortic valve closure.

10. The control device (100) of any one of claims 1 to 9, configured to derive one of the at least one series of trigger signals (σ(t)) from a current supplied to an actuator of the VAD (50).

11. The control device (100) of claim 10, wherein the rotational speed (n ＶＡＤ (t)) from current changes caused by the assisted heart going through its cardiac cycle.

12. 12. A control device (100) according to any one of claims 1 to 11, configured to derive said at least one series of trigger signals (σ(t)) from at least one processed measurement signal, the processed measurement signal representing at least one of the following physical quantities: the pressure difference between the blood ejection outlet of said VAD (50) and the blood intake inlet of said VAD (50), the intraventricular blood pressure of the assisted heart, the aortic blood pressure adjacent to the assisted heart, the vena cava blood pressure adjacent to the assisted heart, the pulmonary artery blood pressure adjacent to the assisted heart.

13. A control device (100) according to any one of claims 1 to 12, configured to derive characteristic information about the circulatory system from at least one of the at least one processed measurement signals within the cardiac cycle, and to derive or predict the at least one characteristic event for a subsequent cardiac cycle based on the characteristic information determined during a preceding cardiac cycle.

14. 14. The control device (100) of claim 13, further comprising: a rotational speed (n) of the VAD (50) from at least two processed measurement signals when deriving or predicting the event. ＶＡＤ (t))と(t ...).

15. 15. The control device (100) according to claim 1, characterized in that during the diastole of the cardiac cycle of the assisted heart, the amount of blood ejected into the aorta or the pulmonary artery is such that the blood volume in the corresponding ventricle is maintained, and that the combined ejection of the VAD (50) and the ventricle during the systole results in a predetermined minimum total peak blood flow (Q ｔｏｔａｌ | ｍａｘ The rotation speed (n (h)) of the VAD (50) is preferably at least 6 L / min, more preferably 8 L / min. ＶＡＤ (t) a control device configured to control the

16. A control device (100) according to any one of claims 1 to 15, characterized in that the rotational speed (n ＶＡＤ(t)) and / or to increase the rotational speed (n ＶＡＤ (t)), in either case preferably at the base speed level (n ＶＡＤ ｓｅｔ，ｂａｓｉｃ (t)) is the control device based on.

17. A control device (100) according to any one of claims 1 to 16, configured to change the rotational speed of the VAD (50) only if it is possible to set a mean VAD-induced blood flow above the minimum blood flow demand currently required by the assisted heart.

18. A VAD (50) for cardiac assistance, comprising a control device (100) according to any one of claims 1 to 17, preferably a non-pulsatile rotary blood pump, the blood pump being preferably of the catheter type.

19. A VAD (50) as claimed in claim 18, which is a low inertia device, having one or more of the following characteristics: the moving parts of the VAD, particularly the rotating parts, such as the rotor or impeller, are made of a lightweight material, such as plastic, and have a low mass; the drive means, such as an electric motor, is located near, preferably in close proximity to, and most preferably adjacent to, the part driven by the motor, such as the rotor or impeller, and if it is of the catheter type, the motor preferably does not have a rotating drive cable or drive wire; the coupling or connection means, such as a shaft, of the motor to the part driven by the motor, such as the rotor or impeller, are short; and all moving parts, particularly the rotating parts, of the VAD have small diameters.

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