阅读说明：本技术 用于控制心脏泵以使心肌氧耗量最小化的系统和方法 (System and method for controlling a heart pump to minimize myocardial oxygen consumption ) 是由 K·苏纳伽瓦 于 2019-07-30 设计创作，主要内容包括：本文公开了用于使用心脏泵治愈急性心肌梗塞(AMI)患者的多种系统、设备和方法,所述心脏泵以在心血管不稳定性存在的情况下使左心室的机械去负荷最大化并使心肌氧耗量(MVO-2)以及相应地梗塞面积最小化的方式受控,以预防随后心力衰竭的发展。在闭合反馈系统中,该系统可以包括被配置为生成用于测量或计算心脏的左心室内的左心室收缩压(LSVP)的输出的传感器以及耦联至心脏泵的控制器。该控制器可以被配置为基于传感器的输出来测量或计算LVSP,并基于测量或计算出的LVSP来控制心脏泵的操作以使左心室的机械去负荷最大化。(Disclosed herein are various systems, devices and methods for healing Acute Myocardial Infarction (AMI) patients using a heart pump to maximize mechanical unloading of the left ventricle and myocardial oxygen consumption (MVO) in the presence of cardiovascular instability 2 ) And correspondingly the minimization of the infarct area, to prevent the subsequent development of heart failure. In a closed feedback system, the system may include a feedback loop configured to generate feedbackA sensor to measure or calculate an output of a left ventricular systolic pressure (LSVP) in a left ventricle of the heart and a controller coupled to the heart pump. The controller may be configured to measure or calculate LVSP based on the output of the sensor and control operation of the heart pump based on the measured or calculated LVSP to maximize mechanical unloading of the left ventricle.)

1. A system for controlling a cardiac pump, comprising:

a sensor configured to generate an output for measuring or calculating Left Ventricular Systolic Pressure (LVSP) within a left ventricle of a heart; and

a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the sensor and control operation of the heart pump to maximize mechanical unloading of the left ventricle based on the measured or calculated LVSP.

2. The system of claim 1, wherein the controller is configured to control one or more of a pump speed and a flow rate of the cardiac pump such that the LVSP in the left ventricle is maintained at a target reference pressure.

3. The system of claim 2, wherein the target reference pressure is set as a fraction of end systolic pressure in a normal ejection beat, wherein the fraction is between about 0.2 and about 0.4.

4. The system of claim 2, wherein the target reference pressure is set as a fraction of mean aortic pressure, wherein the fraction is between about 0.2 and about 0.4.

5. The system of claim 2, wherein the target reference pressure is set to minimize a pressure-volume area (PVA) of the left ventricle.

6. The system of claim 5, wherein the target reference pressure is set to minimize the PVA of the left ventricle by about 90% to about 97%.

7. The system of claim 2, wherein the target reference pressure is set such that myocardial oxygen consumption (MVO) of the left ventricle₂) Most preferablyAnd (5) miniaturization.

8. The system of claim 7, wherein the target reference pressure is set such that the MVO of the left ventricle₂A minimum of about 45% to about 48.5%.

9. The system of any of claims 2-8, wherein the controller is configured to control one or more of pump speed and flow rate of the cardiac pump to maintain the LVSP at the target reference pressure based on a controlled object transfer function that models changes in LVSP in response to changes in pump speed.

10. The system of claim 9, wherein the controlled object transfer function is a second order delay system with a time lag defined as:

where K is the gain, ζ is the damping factor, f_NIs the natural frequency, and L is the time lag.

11. The system of claim 10, wherein the gain K is equal to or about 0.013mmHg/rpm, the damping factor ζ is equal to or about 1.9, the natural frequency f_NEqual to or about 0.41Hz and said time lag L is equal to or about 0.03 seconds.

12. The system of claim 11, wherein the controller is configured to control one or more of a pump speed and a flow rate of the cardiac pump such that the LVSP reaches the target reference pressure in less than a clinically predetermined response time and with less than 10% overshoot of the target reference pressure.

13. The system of claim 11, wherein the controller is configured to control one or more of a pump speed and a flow rate of the cardiac pump to maintain the LVSP at the target reference pressure when a variation of an open loop gain of the controlled object transfer function is 16 times or less than 16 times.

14. The system of claim 11, wherein the controller comprises a proportional-integral controller configured to have a proportional gain equal to about 40, an integral gain equal to about 20, and a derivative gain equal to about 0.

15. The system of claim 11, wherein the controller includes an adaptive control mechanism configured to update the controlled subject transfer function in response to changes in the controlled subject transfer function and reconfigure the controller to control one or more of the pump speed and flow rate of the cardiac pump.

16. A method of treating Acute Myocardial Infarction (AMI) using the system of any one of claims 1-15.

17. A method for treating a patient with Acute Myocardial Infarction (AMI), comprising:

measuring or calculating a Left Ventricular Systolic Pressure (LVSP) within the Left Ventricle (LV) of the heart of a patient, wherein a heart pump is implanted in the heart to mechanically unload blood from the LV to the aorta; and

controlling operation of the cardiac pump to maximize the mechanical unloading of the LV based on a measured or calculated LVSP.

18. A method according to claim 16, wherein controlling operation of the cardiac pump comprises controlling one or more of a pump speed and a flow rate of the cardiac pump such that the LVSP within the LV is maintained at a target reference pressure.

19. The method of claim 17, wherein the target reference pressure is set as a fraction of end systolic pressure in a normal ejection beat, wherein the fraction is between about 0.2 and about 0.4.

20. The method of claim 17, wherein the target reference pressure is set as a fraction of mean aortic pressure, wherein the fraction is between about 0.2 and about 0.4.

21. The method of claim 17, wherein the target reference pressure is set to minimize a pressure-volume area (PVA) of the left ventricle by about 90% to about 97%.

22. The method of claim 17, wherein the target reference pressure is set to cause myocardial oxygen consumption (MVO) of the left ventricle₂) A minimum of about 45% to about 48.5%.

Technical Field

The present disclosure relates to a system for controlling a cardiac pump and related method of treating a patient suffering from Acute Myocardial Infarction (AMI), and in particular to a system for controlling the operation of a cardiac pump to maximize mechanical unloading of the Left Ventricle (LV) and to maximize myocardial oxygen consumption (MVO) during treatment of an AMI patient₂) And therefore a closed feedback control system that minimizes infarct size to prevent the development of long-term heart failure.

Background

AMI, commonly referred to as a heart attack, can be a life-threatening condition that occurs when blood flow to the heart muscle is suddenly cut, causing tissue damage. Dead tissue or infarcts may form in the heart due to insufficient blood supply to the affected area. AMI is typically the result of occlusion of one or more coronary arteries. The coronary arteries carry oxygen-enriched blood to the heart muscle. When these arteries become occluded or narrowed, blood flow to the heart can be significantly reduced or completely stopped.

AMI may require immediate medical treatment to restore blood flow through an occluded artery, sometimes referred to as reperfusion therapy. For example, reperfusion therapy may include procedures to remove or bypass an occlusion, such as Percutaneous Coronary Intervention (PCI), coronary angioplasty, and bypass surgery. Reperfusion therapy may alternatively or additionally include administration of different drugs including, but not limited to, thrombolytic agents, fibrinolytic agents, beta-blockers, and nitroglycerin.

In some AMI patients, a heart pump may be used to stabilize hemodynamics and make it possible to perform safe and effective reperfusion therapy to salvage the affected ischemic myocardium. For example, recent clinical trials and basic studies have shown that LV accessory devices (LVADs) can be used to mechanically unload the LV by drawing blood from the LV and injecting the drawn blood into the aorta. Mechanical unloading can significantly reduce the work performed by the LV and thus reduce MVO₂. It has been observed that MVO₂The reduction in infarct size, i.e., the area of dead tissue resulting from the heart attack, can be reduced. The extent of infarct size reduction generally corresponds to MVO₂Is reduced.

Although mechanical unloading LV has such beneficial effects on AMI, its clinical application has not been established. In patients with chronic heart failure, manually controlling LVAD flow rate (e.g., liters per minute) can achieve stable hemodynamics. However, in AMI patients, cardiac and hemodynamic conditions are inherently unstable because AMI can dramatically change the contractility, vascular resistance, blood pressure, amount of pressure, heart rate, and/or activity of the sympathetic and parasympathetic autonomic nervous systems of the heart over seconds, minutes, or hours. These variability are known to significantly affect hemodynamics. Therapeutic interventions such as drug therapy and reperfusion may further lead to complex dynamic adjustments of these variables and lead to complex hemodynamics.

In the presence of such cardiovascular instability in AMI, it may be difficult (if not impractical) to avoid too much or too little mechanical unloading LV, even if monitoring is done frequently or LVAD flow is continuously adjusted manually with precision. Mechanically unloading the LV at a flow rate that is a bit higher than the fill rate from the pulmonary venous system can cumulatively reduce LV volume and eventually cause suction, collapse the heart, induce life-threatening arrhythmias and severely damage the myocardium. Conversely, mechanically unloading the LV at a flow rate that is slightly less than the fill rate increases LV volume and MVO₂And thus it is difficult to reduce the infarct size of the LV. Thus, manually controlling the heart pump to optimally unload the LV is impractical, ineffective, and potentially life threatening.

Accordingly, there is a need for an improved system and associated method for treating AMI patients using a cardiac pump that is controlled in a manner that optimizes the mechanical unloading of the LV, regardless of the presence of cardiovascular instability, to optimally reduce MVO₂And infarct size.

Disclosure of Invention

The present disclosure relates to systems, devices, and methods for treating AMI patients using a cardiac pump to maximize the mechanical unloading of the LV in the presence of cardiovascular instability, and to minimize MVO₂And correspondingly the minimization of the infarct area, to prevent the subsequent development of heart failure.

In one exemplary embodiment of a system for controlling a cardiac pump, the system includes a sensor configured to generate an output for measuring or calculating a left ventricular systolic pressure (LSVP) within a left ventricle of a heart and a controller coupled to the cardiac pump, and the controller is configured to measure or calculate a LVSP based on the output of the sensor and control operation of the cardiac pump to maximize mechanical unloading of the left ventricle based on the measured or calculated LVSP.

In some embodiments, the controller may be configured to control one or more of the pump speed and flow rate of the cardiac pump such that the LVSP in the left ventricle is maintained at the target reference pressure. The target reference pressure may be set as a fraction of the end systolic pressure in a normal ejection beat (ejection beat), the fraction being between about 0.2 and about 0.4. The target reference pressure may be set to a fraction of the mean aortic pressure that is between about 0.2 and about 0.4. The target reference pressure may be set to minimize the pressure-volume area (PVA) of the left ventricle. For example, in some embodiments, the target reference pressure may be set to minimize the PVA of the left ventricle by about 90% to about 97%. The target reference pressure may be set to cause myocardial oxygen consumption (MVO) of the left ventricle₂) And (4) minimizing. For example, in some embodiments, the target reference pressure may be set such that the MVO of the left ventricle₂A minimum of about 45% to about 48.5%.

In some embodiments, the controller may be configured to control the pump speed and/or flow rate of the cardiac pump to maintain the LVSP at the target reference pressure based on a controlled object transfer function (plant transfer function) that models changes in the LVSP in response to changes in the pump speed. For example, the controlled object transfer function may be a second order delay system with a time lag defined as:

where K is the gain, ζ is the damping factor, f_NIs the natural frequency and L is the time lag. In some embodiments, the gain K may be equal to about 0.013mmHg/rpm, the damping factor ζ may be equal to about 1.9, and the natural frequency f_NMay equal about 0.41Hz and the time lag L may equal about 0.03 seconds.

In some embodiments, the controller may be configured to control the pump speed and/or flow rate of the cardiac pump such that the LVSP reaches the target reference pressure in less than a clinically predetermined response time and with an overshoot of the target reference pressure of less than 10%. When the open loop gain variation of the controlled object transfer function is 16 times or less, the controller may be configured to control the pump speed and/or flow rate of the cardiac pump to maintain the LVSP at the target reference pressure. In some embodiments, the controller may include a proportional integral controller configured to have a proportional gain equal to about 40, an integral gain equal to about 20, and a derivative gain equal to about 0. In some embodiments, the controller may include an adaptive control mechanism configured to update the controlled object transfer function and reconfigure the controller to control the pump speed and/or flow rate of the cardiac pump in response to changes in the controlled object transfer function.

In an exemplary embodiment of a method for treating an Acute Myocardial Infarction (AMI) patient, the method includes measuring or calculating an LSVP within an LV of the patient's heart and controlling operation of a heart pump based on the measured or calculated LVSP to maximize mechanical unloading of the LV. A heart pump is implanted in the heart to perform mechanical unloading of blood from the LV to the aorta.

In some embodiments, controlling operation of the cardiac pump may include controlling one or more of a pump speed and a flow rate of the cardiac pump to maintain the LVSP within the left ventricle at the target reference pressure. The target reference pressure may be set as a fraction of the end systolic pressure in a normal ejection beat, the fraction being between about 0.2 and about 0.4. The target reference pressure may be set to a fraction of the mean aortic pressure that is between about 0.2 and about 0.4. The target reference pressure may be set to minimize the pressure-volume area (PVA) of the left ventricle by about 90% to about 97%. The target reference pressure may be set to cause myocardial oxygen consumption (MVO) of the left ventricle₂) A minimum of about 45% to about 48.5%.

Drawings

The accompanying drawings, which are incorporated herein and constitute part of this specification, illustrate exemplary embodiments and, together with the general description given above and the detailed description given below, serve to explain features of the various embodiments:

fig. 1A illustrates the pressure-volume relationship of the LV during the cardiac cycle using an exemplary pressure-volume loop.

Fig. 1B illustrates an exemplary pressure-volume area (PVA) of the LV and represents the total mechanical work of the LV in a single contraction.

FIG. 2 illustrates PVA and MVO in a single contraction (e.g., per beat)₂A linear relationship therebetween.

Figures 3A-3F illustrate the effect of mechanical unloading of the LV through the heart pump on hemodynamics, pressure-volume loop, PVA and LVSP.

Fig. 4A and 4B are schematic diagrams of an exemplary embodiment of a cardiac pump suitable for mechanical unloading of the LV.

FIG. 5 is a schematic diagram of one exemplary embodiment of a closed feedback cardiac pump control system for controlling a cardiac pump to maximize mechanical unloading of the LV despite the presence of cardiovascular instability.

FIG. 6 illustrates an exemplary step response of an LVSP under control of the feedback cardiac pump control system of FIG. 5.

FIG. 7A illustrates exemplary performance of the feedback cardiac pump control system of FIG. 5 in response to a change in a target reference pressure value.

FIG. 7B illustrates the feedback cardiac pump control system of FIG. 5 in the presence of severe LV volume perturbation on behalf of the MVO₂Exemplary performance in the stabilization of the relevant metric of consumption.

Fig. 8A and 8B illustrate the relationship between the PVA recruitment fraction (recovery fraction) and the LVSP of the fraction to determine the target reference pressure.

FIG. 9 is a schematic diagram of an exemplary embodiment of an adaptive feedback cardiac pump control system.

Detailed Description

Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the systems, devices, and methods disclosed herein. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the systems, devices, and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present disclosure is defined solely by the claims. Features illustrated or described in connection with one exemplary embodiment may be combined with features of other embodiments. Such modifications and variations are intended to be included within the scope of the present disclosure. In the present disclosure, like numbered components of the various embodiments generally have similar characteristics when they have similar properties and/or are used for similar purposes. Those of skill in the art will understand, in light of the present disclosure, various examples in which like numbered elements in the various figures are similar.

The present disclosure relates to systems, devices, and methods for treating AMI patients using a cardiac pump that can maximize the mechanical unloading of the LV in the presence of cardiovascular instability and maximize the MVO₂And correspondingly the minimization of infarct area, to prevent the subsequent development of heart failure.

Fig. 1A illustrates the pressure-volume relationship of the LV during the cardiac cycle. Each of the pressure-volume loops 110 and 120 represents approximate LV pressure and LV volume measurements during the entire cardiac cycle. The cardiac cycle or heartbeat can be divided into four basic phases: ventricular filling 110a, isovolumetric contraction 110b, systolic ejection 110c, and isovolumetric relaxation 110 d. As is well known, end-systolic pressure is linearly related to end-systolic volume and is represented as the end-systolic pressure-volume relationship (ESVPR, line 130). ESPVR is substantially insensitive to changes in load conditions and its slope represents well the contractility of the ventricles.

Fig. 1B illustrates an exemplary pressure-volume area (PVA) of the LV and represents the total mechanical work of the LV in a single contraction. PVA is a specific region bounded by ESPVR and end-diastolic pressure-volume curve (EDPVR) and the Systolic Segment (SS) of the pressure-volume trajectory in systole. Geometrically in the pressure-volume plane, PVA is the sum of the External Work (EW) and Potential Energy (PE), i.e. PVA ═ PE + EW. As shown in FIG. 1A, the PVA of the cardiac cycle can be reduced by reducing LV end-systolic pressure (LVSP) and thereby reducing the overall mechanical work of the ventricles. For example, decreasing LVSP from LVSP 112 to LVSP 122 decreases PVA (e.g., PVA 115 to PVA 125). As discussed herein, a cardiac pump may be used to reduce LVSP by reducing LV volume.

FIG. 2 illustrates PVA and MVO in a single contraction (e.g., per beat)₂A linear relationship therebetween. As is well known, PVA and MVO₂Linear correlation (line 210). Thus, reduction of PVA (e.g., PVA 220 through PVA 222) reduces MVO₂(e.g., MVO)₂230 to MVO₂232). It has been observed that MVO₂The reduction in (b) can reduce the infarct size or the area of dead tissue resulting from a heart attack.

Figures 3A-3F illustrate the effect of LV mechanical unloading by a heart pump on hemodynamics, pressure-volume loop, PVA and LVSP. For example, fig. 3A, 3B, and 3C illustrate exemplary changes in LV pressure (LVP) and Aortic Pressure (AP) over a time series for different mechanical unloading levels of the LV. Fig. 3D illustrates exemplary pressure-volume loops Lo (no mechanical load relief), Lp (partial mechanical load relief) and LMAX (maximum mechanical load relief) corresponding to various changes in LVP. FIG. 3A illustrates the situation when there is no mechanical unloading by the heart pumpMoreover exemplary LV pressure (LVP) and Aortic Pressure (AP). Partial mechanical unloading may lower aortic pulse pressure as shown in fig. 3B, but the LV is still shooting blood as shown by the pressure-volume loop Lp in fig. 3D. When the mechanical unloading is at a maximum, the LV is no longer ejecting blood, as shown by the pressure-volume loop Lmax in fig. 3D, and LV pressure LVP is lower than aortic pressure AP, as shown in fig. 3C. FIG. 3E shows that the maximum load shedding can be PVA (PVAMAX) and thus MVO₂Is very small. In AMI, the maximum load shedding is a condition in which the infarct size becomes minimum. However, as shown in the normal and AMI canine models of LVSPo and LVSPAMI in fig. 3F, mechanical unloading may cause an almost sudden and dramatic drop in LVSP even under relatively stable hemodynamic conditions. In AMI conditions, it may be impractical, if not impossible, to maintain maximum unloading by manually controlling the heart pump, since cardiac and hemodynamic conditions can be extremely dynamic and can vary widely. Accordingly, disclosed herein are embodiments of a closed feedback control system for a cardiac pump that may be configured to maintain a predetermined target LVSP during mechanical unloading in the presence of hemodynamic instability inherent to AMI conditions.

Fig. 4A and 4B are schematic diagrams of an exemplary embodiment of a cardiac pump 400 suitable for mechanical unloading of the LV. In an illustrative embodiment, the heart pump 400 may include an impeller pump 410, a pump motor 412, a blood inlet 414, and a blood outlet 416. In some embodiments, the pump 400 may be disposed in the catheter 420 such that the cardiac pump 400 may be inserted through a standard catheterization procedure. For example, the heart pump 400 may be inserted through the femoral artery into the ascending aorta 10, through the aortic valve 15, and into the left ventricle 20. A pressure sensor 430 may be disposed within the conduit 420 to measure LVSP during pump operation. In some embodiments, another pressure sensor 432 may be disposed within the catheter 420 to measure aortic pressure. In some embodiments, without pressure sensor 430 in the left ventricle, pressure sensor 432 used to measure aortic pressure and/or differential pressure may be used to calculate LVSP during pump operation. The conduit 420 may also serve as a conduit (conduit) to facilitate wired connections from a remote control or console (e.g., the pump controller 510 of fig. 5) to the pump motor 412 and to the pressure sensors 430, 432 or both.

As shown, the pump 400 may pull blood from the LV 20 into the impeller pump 410 through a blood inlet 414 and discharge the blood into the ascending aorta 10 through a blood outlet 416. The flow rate of the cardiac pump 400 may be controlled based on the speed of the pump motor 412, and as discussed in more detail below, the speed of the pump motor 412 may be controlled based on measurements obtained from the LVSP sensor 430 and optionally the aortic pressure sensor 432. In some embodiments, the heart pump 400 may pump up to 5.0 liters of blood per minute from the LV to the aorta. In some embodiments, the cardiac pump 400 may pump at a flow rate of greater than or less than 5.0 liters per minute. Examples of cardiac pumps suitable for use in various embodiments may include those from Abiomed, inc, located headquarters in denvers, massachusettsFamily of cardiac pumps, including but not limited to ImpellaImpellaImpellaAnd ImpellaOne of ordinary skill will readily appreciate that other left ventricular assist devices or heart pumps may be used.

While various cardiac pumps are capable of unloading the left ventricle, a pump that can produce a cardiac output sufficient to support (i.e., perfuse) the entire body of an AMI patient may be useful. This is because LV requires periodic cessation of ejection in order to minimize PVA. This condition may result in flow being generated at a cardiac pump used for mechanical unloadingTo be achieved when perfusing the whole body. PVA and MVO can be adjusted by controlling the heart pump flow rate once the LV stops ejection periodically₂And (4) minimizing. Various embodiments of the cardiac pump control system disclosed herein may be used with a cardiac pump capable of producing cardiac output to support the entire body.

FIG. 5 is a schematic diagram of an exemplary embodiment of a closed feedback cardiac pump control system 4500, which closed feedback cardiac pump control system 4500 is used to control a cardiac pump to maximize mechanical unloading of the left ventricle despite the presence of cardiovascular instability. In the illustrated embodiment, the system 500 may include a cardiac pump 400, a pump controller 510, a LVSP pressure sensor 430, and optionally an aortic pressure sensor 432. As discussed above with respect to fig. 4B, the heart pump 400 may be placed within the heart to mechanically unload blood from the left ventricle into the aorta.

The pump controller 510 may be configured to control the flow rate of the pump 410 by adjusting the speed (e.g., revolutions per minute or RPM) of the pump motor 412. The pump controller 510 can send commands or signals over a wired or wireless connection to adjust the speed of the pump motor 412 so that the pump 410 mechanically unloads the left ventricle at a target flow rate (e.g., liters per minute) set by a target pressure.

In some embodiments, the pressure sensors 430 and/or 432 may be configured to generate outputs that are used by the pump controller 510 to measure or calculate LVSP within the LV of the heart. For example, in some embodiments, the pressure sensor 430 may be configured to measure the LSVP and output it as a feedback signal to the pump controller 510. The pump controller 510 can use LVSP as feedback information to speed adjust the pump motor 412 so that the pump flow rate can maintain LVSP at or near a target reference pressure that is less than normal LVSP and thus well below the mean aortic pressure. In some embodiments, the target reference pressure may be set to the pump controller 510 by manual input. In some embodiments, the target reference pressure may be set to a calculated value obtained or determined by the pump controller 510.

To automatically controlCardiac pump to minimize PVA and thus MVO₂The pump controller 510 (sometimes referred to herein as a feedback controller) may be configured to control the speed, flow rate, or other operating characteristics of the cardiac pump to bring the LVSP at a low reference pressure level, regardless of significant changes in the cardiac or hemodynamic conditions. This can be achieved when the open loop gain of the feedback controller is large enough to stabilize LVSP fluctuations caused by AMI-related severe cardiac and hemodynamic instability. In some embodiments, the feedback controller of the cardiac pump is stable with no oscillations (or virtually no oscillations) in the presence of severe cardiac and hemodynamic instability. Control theory indicates that the higher the open loop gain, the lower the stability of the closed loop feedback system. Accordingly, in some embodiments, the pump controller 510 may be configured to balance open loop gain with system stability.

To develop a high open-loop gain feedback controller without compromising stability, an open-loop transfer function may be determined for the controlled object to be controlled. The controlled object may represent a heart augmented with a heart pump. For example, in some embodiments, the controlled object may model the dynamic changes in the LVSP in response to changes in the pump speed of the heart pump used for mechanical unloading. For example, a subject may be defined as a single-input single-output (SISO) system, where the input is a pump speed control command (e.g., rpm) and the output is LVSP (e.g., mmHg). In cardiovascular physiology, it has never been investigated how pump speed changes dynamically affect the transfer function of LVSP. In some embodiments, other inputs may be used to define the transfer function of the controlled object, such as flow rate (e.g., milliliters per second) or other operating characteristics of the heart pump. In some embodiments, other outputs may be used to define a transfer function of the controlled object, such as LV diastolic pressure, aortic pressure, or other properties of the cardiovascular system (e.g., heart) that may be measured or estimated using sensors (e.g., sensors 430, 432).

In some embodiments, a computational model of the cardiovascular system may be employed to estimate an approximate transfer function from pump speed to LVSP. In some embodiments, the transfer function may be approximated and reduced to a second order system with delay, such as:

four of the parameters are gain K, damping factor ζ and natural frequency f_NAnd a delay time L. The term j represents the imaginary part, where j²Is-1. Since the second order transfer function h (f) originates from the basic anatomy of the cardiovascular system, the transfer function can be applied to many species with similar anatomy to the human cardiovascular system. The transfer function h (f) may also be used as a controlled object for modeling a heart with cardiac pump enhancement in a disease state, since such conditions are unlikely to involve severe anatomical changes of the cardiovascular system.

In some embodiments, the four parameters of the object transfer function h (f) may include a gain K equal to or about 0.013mmHg/rpm, a damping factor ζ equal to or about 1.9, a natural frequency f equal to or about 0.41Hz, and a frequency of the object transfer function h (f)_NA delay time L equal to or about 0.03 seconds. As discussed below with respect to fig. 9, in some embodiments, the values of one or more parameters of the controlled object transfer function h (f) may be changed in response to changes in AMI and volume load conditions. Although the approximation of the foregoing parameters is based on animal experiments and canine models in the AMI setting, one of ordinary skill in the art will recognize that these parameters can be adjusted to accommodate any changes associated with the human cardiovascular system.

Based on the identified controlled subject transfer function h (f), the pump controller 510 may be configured to keep LVSP at a constant value regardless of changes in cardiac and hemodynamic conditions. For example, as shown in fig. 5, in some embodiments, the pump controller 510 may include a comparator 512 and a proportional-integral (PI) controller or a proportional-integral-derivative (PID) controller 514. The comparator 512 may be coupled to the pressure sensor 430 and configured to receive a measurement of the LSVP output from the pressure sensor. The comparator 512 may be configured to compare the target reference pressure with the LVSP measured within the left ventricle and output a pressure differential or error signal e (t) to the PID controller 514.

The PID controller may be configured to implement the following equation:

wherein K_pIs the proportional gain, K_iIs the integral gain, K_dIs the derivative gain, t is the time or instant time, τ is the integral variable whose value is from time 0 to the current time t. The integral term may be configured such that the gain of the controller is infinity, in practice equal to infinity. Equation u (t) may be rewritten in the Laplace domain as u(s) ═ K_p+K_iS and K_ds。

Can select K_p、K_iAnd K_dIs used to tune the system 500 so that the time or frequency response of the LVSP of the closed loop system can be optimized with respect to the step change in pump speed or corresponding flow rate. For example, in some embodiments, K may be selected_p、K_iAnd K_dSuch that the measured LVSP can reach the target reference pressure with minimal overshoot and time delay in response to a corresponding adjustment in pump speed. For example, in some embodiments, (i) the overshoot of the LVSP step response under closed loop conditions may be less than about 10%, (ii) the time to reach the LVSP steady state response may be less than a predetermined clinically relevant response time (e.g., about 60 seconds), and/or (iii) the steady state deviation from the target pressure may average to zero. In some embodiments, the PID controller 514 can be implemented such that the feedback control system 500 is stable and can satisfy one or more such constraints if the open loop gain of the controlled object varies (e.g., up to a maximum) by up to or more than 16 times.

In some embodiments, based on the transfer function of the identified controlled object h (f), the minimum implementation of the controller may be to have a proportional gain K equal to or about 40_pAn integral gain K equal to or about 20_iAnd a proportional-integral (PI) controller having a derivative gain KJ equal to or about 0. Gain K_pAnd K_iMay be combined with each otherSuch that the system maintains LVSP at a constant value in the presence of AMI-induced severe instability of cardiac and hemodynamic conditions, including changes in open loop gain of the controlled subject, e.g., up to or exceeding equal to or about 16 times. In some embodiments, each gain parameter K_p、K_iAnd K_dMay be adjusted in response to changes in design requirements and/or open loop gain of the object.

Fig. 6 illustrates an exemplary step response of an LVSP under control of the closed feedback cardiac pump control system 500 of fig. 5 using the controller parameters described above. For example, as shown, the control system 500 may provide a step response 610 for the LVSP, the step response 610 exhibiting no overshoot under AMI conditions and reaching steady state within approximately 20 seconds. When the controlled object exhibits an open loop gain that is 4 times greater than normal, the control system 500 can provide a step response 620 to the LVSP, the step response 620 exhibiting an overshoot of less than about 5% and reaching steady state in less than about 20 seconds. When the controlled object exhibits an open loop gain that is one-quarter (1/4) times the normal value, the control system may provide a step response 630 to the LVSP, where the step response 630 exhibits no overshoot and reaches steady state in about 40 seconds.

Based on extensive animal experiments performed under extreme AMI conditions, it was observed that the open loop gain of controlled subjects varied in the range of 4 to 1/4-fold. In clinical applications, the open loop gain variation associated with human patients should not exceed 16-fold. It takes about 20 to 40 seconds to reach a steady state step response that should be sufficient to avoid adverse effects in the results associated with ventricular unloading therapy. However, those skilled in the art will recognize that the control system may be configured to reach steady state at other clinically relevant response times.

Fig. 7A and 7B illustrate exemplary performance of the closed feedback cardiac pump control system of fig. 5 using pump speed to control LVSP. For example, FIG. 7A illustrates when the target reference pressure LVSP is input_INWhen stepped from 40, 70, and 40mmHg, control system 500 may adjust commanded pump speed S to provide output LVSP that follows the target pressure_OUT. FIG. 7A also shows the correlation with the controlled output LVSPOutput arterial pressure AP_OUTAnd LV volume LVV_OUTA change in (c).

FIG. 7B shows an MVO representing an LV in the presence of severe volume perturbation (e.g., an increase or decrease in left ventricular volume)₂Stability of relevant indicators of consumption (e.g., LVSP and PVA). Volume perturbation is an inherent hemodynamic instability of AMI. As shown in fig. 7B, despite severe changes in volume (e.g., ± 8ml/kg), LVSP and PVA may be held substantially constant to maintain a target LVSP by controlling the pump speed of a cardiac pump (e.g., 400) using an embodiment feedback control system 500. In contrast, LVSP and PVA can change significantly in response to severe volume perturbations of the LV using a fixed speed cardiac pump.

In some embodiments, where a faster or more stable response is desired depending on the purpose, one of ordinary skill in the art will recognize that the gain parameter K of the PID controller 514_p、K_iAnd K_dOne or more of which may be adjusted. Thus, although specific gain parameter values for a PID controller are disclosed herein, these values are exemplary and not limiting.

As described above, the cardiac pump control system 500 of an embodiment may be configured to maintain LVSP at the MVO determined to be the LV₂Minimized target reference pressure. For example, as shown in FIGS. 1 and 2, MVO can be achieved by PVA that minimizes LV₂And (4) minimizing. Theoretically, zero PVA could result in MVO₂And minimum. However, keeping PVA at zero (which means LVSP of zero mmHg) is difficult to achieve safely and stably, as even a small drop in LVSP below zero can result in the pump creating severe suction within the LV that can damage the heart. Thus, in some embodiments, the closed feedback cardiac pump control system 500 of fig. 5 may be configured to maintain LVSP at a target LVSP that provides approximately a minimum MVO₂And still be safely and stably controllable by the feedback system. For example, in some embodiments, as shown in fig. 8A and 8B, a target LVSP may be determined based on the relationship between the fractional LVSP and the recruitment fractional PVA.

Fig. 8A illustrates the relationship between fractional LVSP and fractional LV volume. As shown, in normal ejection contractions, pressure and volume are normalized to unity at end-systole. Fractional LVSP "α" is the ratio of LVSP to end systolic pressure at normal ejection during unloading, which defines the operating condition of LV unloading. The lower the fraction LVSP α, the stronger the load shedding. For a given fraction of LVSP α, a fractional LV volume also becomes the cause, since the LV volume has been normalized by the end systolic volume. The LV end-diastolic volume is given by 1/(1-. beta.), where β is the LV ejection fraction, i.e., stroke volume divided by the end-diastolic volume.

The recruited PVA was one recruited by LV workload under operating conditions of α. The residual PVA is the PVA remaining by unloading under the operating conditions of α. Fractional PVA recruitment is defined by the ratio of residual PVA to the sum of the recruited PVA and residual PVA, which represents the percentage of total PVA recruited by LV workload. Mechanical unloading can reduce the fraction of LVSP α, increase the recruited PVA, and result in a reduction in residual PVA of LV.

FIG. 8B illustrates the fraction of PVA recruitment as a function of the fraction of LVSP "α" at various ejection fractions "β". As shown, fractional PVA recruitment decreased with fractional LVSP α. For example, at α ═ 1 (i.e., where the fractional LV volume is 1), fractional PVA recruitment 806, 804, and 802 equal 0.75, 0.57, and 0.33, respectively, for ejection fractions β of 0.6, 0.4, and 0.2. This means that LVs with poor shrinkage may require more unloading to reduce PVA. For α -0.4, the fraction of PVA recruitment 806', 804', 802' may be greater than or equal to 0.9, regardless of ejection fraction β. For α ═ 0.2, the fraction of PVA recruitment 806 ", 804", 802 "may be greater than or equal to 0.97, regardless of ejection fraction β.

Thus, in some embodiments, the target LVSP may be set equal to the product of the end systolic pressure at normal ejection beats and the fractional LVSP α, where the value of α is between about 0.2 and about 0.4, to minimize PVA of the LV by about 90% to 97%. During normal ejection beats, the end-systolic pressure is typically between 70 and 110 mmHg. Under the control of the feedback system 500 of the embodiment of FIG. 5, by using a heart pumpMechanical unloading, the target LVSP within this range can be safely and stably achieved. Assume MVO of 50%₂Is PVA-independent, a PVA reduction of about 90% to 97% can be converted to MVO, respectively₂A corresponding reduction of about 45% to 48.5%. MVO in the presence of significant noise in assessing infarct size₂Small differences in (a) are unlikely to affect infarct size. MVO₂This reduction in oxygen can achieve significant oxygen savings and thereby reduce infarct size and subsequent heart failure.

In some embodiments, the target LVSP may be set equal to the product of the mean aortic pressure and a fractional LVSP α, where the value of α is between about 0.2 and about 0.4, to minimize PVA of the LV by about 90% to about 97%. As mentioned above, assume an MVO of about 50%₂Is PVA-independent, a PVA reduction of about 90% to 97% may correspond to MVO₂From about 45% to about 48.5%. MVO₂This reduction in oxygen can achieve significant oxygen savings and thereby reduce infarct size and subsequent heart failure.

In some embodiments, where the blood dynamics of the AMI patient are relatively stable (including aortic pressure), the target reference pressure (e.g., target LSVP) may be set to a fixed fraction of the mean aortic pressure, such as, but not limited to, a fraction between about 0.2 to about 0.4. In some embodiments, the target reference pressure may be set as a fixed fraction of other hemodynamic parameters that may be measured or estimated. Once the target pressure is set, it does not change until clinical necessity arises. This simplifies setting the target pressure according to the patient hemodynamic condition.

FIG. 9 is a schematic diagram of an exemplary embodiment of an adaptive feedback cardiac pump control system 900. As shown, the control system 900 can include a comparator 905, an adaptive pump controller 910, a cardiac pump actuator 920, a controlled object model 930, one or more sensors 940, a system identification module 950, and a controller design module 960. The control system 900 may be substantially similar to the control system 500 described above with respect to fig. 4 and 5, except as described below or as would be readily understood by one of ordinary skill in the art. A detailed description of the structure and function thereof is thus omitted herein for the sake of brevity. The control system 900 may include any one or more of the features of the control system 500 described above.

In some embodiments, the adaptive feedback cardiac pump control system 900 can be used to control a cardiac pump to maintain a target LVSP or AP in an AMI patient that may require more complex mechanical unloading applications. For example, in patients with right ventricular failure, life-threatening heart rhythms, and with other mechanical circulatory devices, more complex mechanical unloading applications may be desirable. Thus, a feedback cardiac pump control system configured to control a controlled object in relation to a fixed transfer function may not guarantee that LVSP and PVA are at a constant. Accordingly, the system identification module 950 and the controller design module 960 can be used to adaptively configure the control system 900 to control the cardiac pump 920 based on continuously and/or periodically identifying and updating the controlled object model 930 representing the heart augmented with the cardiac pump (e.g., 400). In this way, the adaptive pump controller 910 may be adaptively configured to adaptively configure PVA and MVO in patients with AMI under a variety of pathological conditions₂And (4) minimizing.

In some embodiments, the system identification module 950 may be configured to periodically or continuously monitor and update the controlled object transfer function, and the controller design module 960 may be configured to update one or more parameters of the adaptive pump controller 910 in response to a determined change in the controlled object transfer function. For example, in some embodiments, the system identification module 950 may be configured to adjust one or more parameters of the second order transfer function h (f) of the subject, such as the gain K, the damping factor ζ, the natural frequency f, in response to a change in correlation between the pump speed and LVSP_NAnd/or a delay time L. In some embodiments, the system identification module 940 may be configured to model the controlled object using a transfer function other than the second order transfer function h (f). In some embodiments, the system identification module 950 may be configured to change the controlled object transfer function based on the LVSP sensor measurements in response to changes in pump speed.

Based on the determined change in the controlled object transfer function,the controller design module 960 may adjust one or more parameters of the adaptive pump controller 910. For example, where the adaptive pump controller is a PI or PID controller, the controller design module 960 may adjust a proportional gain K associated with the controller_pIntegral gain K_iAnd a differential gain K_dOne or more of the above. Can select K_p、K_iAnd K_dSuch that the measured LVSP can reach the target reference pressure with minimal overshoot and time delay in response to a corresponding adjustment in pump speed.

The various illustrative logical blocks, modules, circuits, and algorithm operations described in connection with the embodiments disclosed herein may be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and operations have been described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. Skilled artisans may implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the claims.

The hardware used to implement the various illustrative logics, logical blocks, modules, and circuits described in connection with the aspects disclosed herein may be implemented or performed with a general purpose processor, a Digital Signal Processor (DSP), an Application Specific Integrated Circuit (ASIC), a Field Programmable Gate Array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware (discrete hardware) components, or any combination thereof designed to perform the functions described herein. A general purpose processor may be a microprocessor, but in the alternative, the processor may be any conventional processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of receiver smart objects (receiver smart objects), e.g., a combination of a DSP and a microprocessor, two or more microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration. Alternatively, some operations or methods may be performed by circuitry for a given function.

In one or more aspects, the functions may be implemented in hardware, software, firmware, or any combination thereof. If implemented in software, the functions may be stored as one or more instructions or code on a non-transitory computer-readable storage medium or a non-transitory processor-readable storage medium. The operations of the methods or algorithms disclosed herein may be embodied in processor-executable software modules or processor-executable instructions, which may reside on non-transitory computer-readable or processor-readable storage media. A non-transitory computer-readable or processor-readable storage medium may be any storage medium that is accessible by a computer or a processor. By way of example, and not limitation, such non-transitory computer-readable or processor-readable storage media can comprise RAM, ROM, EEPROM, flash memory, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage smart objects, or any other medium that can be used to store desired program code in the form of instructions or data structures and that can be accessed by a computer. Disk and disc (disc), as used herein, includes Compact Disc (CD), laser disc, optical disc, Digital Versatile Disc (DVD), floppy disk and blu-ray disc where disks usually reproduce data magnetically, while discs reproduce data optically with lasers. Combinations of the above are also included within the scope of non-transitory computer-readable and processor-readable media. Additionally, the operations of a method or algorithm may reside as one or any combination or set of codes and/or instructions on a non-transitory processor-readable storage medium and/or computer-readable storage medium, which may be incorporated into a computer program product.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the claims. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the scope of the claims. Thus, the present disclosure is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the following claims and the principles and novel features disclosed herein.