Systems and methods for controlling heart pump to minimize myocardial oxygen consumption

Abstract

To provide systems, devices and methods for curing acute myocardial infarction (AMI) patients using a heart pump controlled in a manner that maximizes mechanical unloading of the left ventricle in the presence of cardiovascular instability and minimizes myocardial oxygen consumption (MVO2) and consequentially infarct size to prevent the development of subsequent heart failure.SOLUTION: A closed feedback system can include a sensor configured to generate an output used to measure or calculate a left ventricular systolic pressure (LSVP) within the left ventricle of a heart, and a controller coupled to a heart pump. The controller can be configured to measure or calculate the LVSP based on the output of the sensor and to control an operation of the heart pump to maximize mechanical unloading of the left ventricle based on the measured or calculated LVSP.SELECTED DRAWING: Figure 3-1

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit of U.S. patent application Ser. No. 16 / 050,542, entitled "Systems and Methods for Controlling a Heart Pump to Minimize Myocardial Oxygen Consumption," filed July 31, 2018, the entire contents of which are incorporated herein by reference.

[0002] Field The present disclosure relates to a system for controlling a heart pump and related methods for treating patients with acute myocardial infarction (AMI), and in particular to a closed-feedback control system for controlling the operation of the heart pump to maximize left ventricular (LV) mechanical unloading and minimize myocardial oxygen consumption (MVO2) and consequently infarct size during treatment of AMI patients, thereby preventing the development of long-term heart failure. [Background technology]

[0003] background AMI, commonly known as a heart attack, can be a life-threatening condition that occurs when blood flow to the heart muscle is suddenly blocked, causing tissue damage. Inadequate blood supply to the affected area can lead to the formation of necrotic tissue, or an infarct, in the heart. AMI is usually the result of a blockage in one or more of the coronary arteries. Coronary arteries carry oxygen-rich blood to the heart muscle. When these arteries become blocked or narrowed, blood flow to the heart is significantly reduced or completely stopped.

[0004] AMI may require immediate medical treatment to restore blood flow through the blocked artery (also called reperfusion therapy). Reperfusion therapy may include surgical procedures to remove or circumvent the blockage, such as percutaneous coronary intervention (PCI), coronary angioplasty, and bypass surgery. Reperfusion therapy may alternatively or additionally include the administration of various drugs, including thrombolytics, fibrinolytics, beta-blockers, and nitroglycerin.

[0005] In some patients with AMI, a cardiac pump can be used to stabilize hemodynamics and perform safe and effective reperfusion therapy to salvage the affected ischemic myocardium. For example, recent clinical trials and basic research have demonstrated that an LV assist device (LVAD) can be used to mechanically unload the LV by withdrawing blood from the LV and injecting it into the aorta. Mechanical unloading can significantly reduce the work performed by the LV and thus reduce MVO2. It has been shown that a reduction in MVO2 can reduce infarct size, i.e., the area of ​​necrotic tissue resulting from a heart attack. The degree of infarct size reduction generally parallels the reduction in MVO2.

[0006] Despite the beneficial effects of LV mechanical unloading during AMI, its clinical application has yet to be established. In patients with chronic heart failure, manual control of LVAD flow (e.g., liters per minute) can achieve stable hemodynamics. However, in patients with AMI, the cardiac and hemodynamic status are inherently unstable because AMI can significantly alter myocardial contractility, vascular resistance, blood pressure, stressed blood volume, heart rate, and / or sympathetic and parasympathetic autonomic nervous system activity over time, from seconds to minutes to hours. These variabilities are known to significantly affect hemodynamics. Therapeutic interventions, such as drug therapy and reperfusion, can further induce complex dynamic modulations of these variables, resulting in complex hemodynamics.

[0007] In the presence of such cardiovascular instability in AMI, preventing over- or under-unloading of the LV is difficult, if not impractical, even with constant monitoring or continuous manual precision adjustment of LVAD flow. Mechanical unloading of the LV at a flow rate slightly higher than the filling rate coming from the pulmonary venous system cumulatively reduces LV volume and ultimately induces aspiration, which can collapse the heart, cause life-threatening arrhythmias, and severely damage the myocardium. Conversely, mechanical unloading of the LV at a flow rate slightly lower than the filling rate increases LV volume and MVO2, thereby making it difficult to reduce LV infarct size. Therefore, manual control of the heart pump to optimally unload the LV is impractical, ineffective, and potentially life-threatening.

[0008] Therefore, there is a need for improved systems and related methods for treating AMI patients using a cardiac pump that is controlled in a manner that optimizes LV mechanical unloading despite the presence of cardiovascular instability, thereby optimally reducing MVO2 and infarct size. Summary of the Invention

[0009] overview The present disclosure relates to various systems, devices, and methods for treating AMI patients using a cardiac pump controlled in a manner that maximizes LV mechanical unloading in the presence of cardiovascular instability, minimizes MVO2 and consequently infarct size, and prevents the subsequent development of heart failure.

[0010] In one exemplary embodiment of a system for controlling a heart pump, the system includes a sensor configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) in a left ventricle of the 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 to control operation of the heart pump to maximize mechanical unloading of the left ventricle based on the measured or calculated LVSP.

[0011] In some embodiments, the control device can be configured to control one or more of the pump speed and flow rate of the heart pump so that the LVSP in the left ventricle is maintained at a target reference pressure. The target reference pressure can be set to a ratio of the end-systolic pressure at normal pumping, the ratio being about 0.2 to about 0.4. The target reference pressure can be set to a ratio of the mean aortic pressure, the ratio being about 0.2 to about 0.4. The target reference pressure can be set to minimize the pressure-volume area (PVA) of the left ventricle. For example, in some embodiments, the target reference pressure can be set to minimize the PVA of the left ventricle by about 90% to about 97%. The target reference pressure can be set to minimize the myocardial oxygen consumption (MVO2) of the left ventricle. For example, in some embodiments, the target reference pressure can be set to minimize the MVO2 of the left ventricle by about 45% to about 48.5%.

[0012] In some embodiments, the controller can be configured to control the pump speed and / or flow rate of the heart pump to maintain the LVSP at the target reference pressure based on a plant transfer function that models changes in LVSP in response to changes in pump speed. For example, in some embodiments, the plant transfer function is TIFF2025124788000002.tif13128 (where K is the gain, ζ is the damping coefficient, and f N is the natural frequency and L is the time lag) In some embodiments, the gain K can be equal to about 0.013 mmHg / rpm, the damping coefficient ζ can be equal to about 1.9, and the natural frequency f N can be equal to about 0.41 Hz, and the time lag L can be equal to about 0.03 seconds.

[0013] In some embodiments, the controller can be configured to control the pump speed and / or flow rate of the heart pump so that the LVSP reaches the target reference pressure in less than a clinically determined response time and with less than 10% overshoot of the target reference pressure. The controller can be configured to control the pump speed and / or flow rate of the heart pump so as to maintain the LVSP at the target reference pressure when the open-loop gain of the plant transfer function changes by no more than 16 times. In some embodiments, the controller can include a proportional-integral controller configured with 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 can include an adaptive control mechanism configured to update the plant transfer function and reconfigure the controller to control the pump speed and / or flow rate of the heart pump in response to changes in the plant transfer function.

[0014] In one exemplary embodiment of a method for treating an acute myocardial infarction (AMI) patient, the method includes measuring or calculating LVSP in the LV of the patient's heart, and controlling operation of a heart pump to maximize mechanical unloading of the LV based on the measured or calculated LVSP. The heart pump is implanted in the heart to perform mechanical unloading of blood from the LV to the aorta.

[0015] In some embodiments, controlling the operation of the heart pump can include controlling one or more of the pump speed and flow rate of the heart pump so that the LVSP in the left ventricle is maintained at a target reference pressure. The target reference pressure can be set to a ratio of the end-systolic pressure at normal pumping, where the ratio is about 0.2 to about 0.4. The target reference pressure can be set to a ratio of the mean aortic pressure, where the ratio is about 0.2 to about 0.4. The target reference pressure can be set to minimize the pressure-volume area (PVA) of the left ventricle by about 90% to about 97%. The target reference pressure can be set to minimize the myocardial oxygen consumption (MVO2) of the left ventricle by about 45% to about 48.5%. [The present invention 1001] a sensor configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) within a left ventricle of the heart; a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the sensor and to control operation of the heart pump to maximize mechanical unloading of the left ventricle based on the measured or calculated LVSP; 1. A system for controlling a heart pump, comprising: [The present invention 1002] The system of the present invention 1001, wherein the control device is configured to control one or more of the pump speed and flow rate of the heart pump so that the LVSP in the left ventricle is maintained at a target reference pressure. [The present invention 1003] The system of the present invention 1002, wherein the target reference pressure is set to a ratio of the end-systolic pressure in normal ejection, and the ratio is about 0.2 to about 0.4. [The present invention 1004] The system of the present invention 1002, wherein the target reference pressure is set to a ratio of the mean aortic pressure, and the ratio is about 0.2 to about 0.4. [The present invention 1005] The system of the present invention 1002, wherein the target reference pressure is set to minimize the pressure-volume area (PVA) of the left ventricle. [The present invention 1006] The system of the present invention 1005, wherein the target reference pressure is set to minimize the left ventricular PVA by approximately 90% to approximately 97%. [The present invention 1007] The system of the present invention 1002, wherein the target reference pressure is set to minimize myocardial oxygen consumption (MVO2) of the left ventricle. [The present invention 1008] The system of the present invention 1007, wherein the target reference pressure is set to minimize the left ventricular MVO2 by approximately 45% to approximately 48.5%. [The present invention 1009] Any of the systems of the present inventions 1002-1008, wherein the controller is configured to control one or more of the pump speed and flow rate of the cardiac pump to maintain the LVSP at a target reference pressure based on a plant transfer function that models changes in LVSP in response to changes in pump speed. [The present invention 1010] If the plant transfer function is TIFF2025124788000003.tif13128 (where K is the gain, ζ is the damping coefficient, and f N is the natural frequency and L is the time lag) The system of the present invention 1009 is a second-order delay system having a time lag, defined as follows: [The present invention 1011] The gain K is approximately equal to 0.013 mmHg / rpm, the damping coefficient ζ is approximately equal to 1.9, and the natural frequency f N is equal to about 0.41 Hz and the time lag L is equal to about 0.03 seconds. [The present invention 1012] The system of the present invention 1011, wherein the control device is configured to control one or more of the pump speed and flow rate of the heart pump so that the LVSP reaches the target reference pressure in less than a clinically determined response time and with less than 10% overshoot of the target reference pressure. [The present invention 1013] The system of the present invention 1011, wherein the control device is configured to control one or more of the pump speed and flow rate of the heart pump to maintain the LVSP at the target reference pressure when the open loop gain of the plant transfer function changes by 16 times or less. [The present invention 1014] The control device A proportional-integral controller consisting of a proportional gain equal to approximately 40, an integral gain equal to approximately 20, and a derivative gain equal to approximately 0. The system of the present invention 1011 includes: [The present invention 1015] The control device an adaptive control mechanism configured to update a plant transfer function and reconfigure the controller to control one or more of a pump speed and a flow rate of the heart pump in response to changes in the plant transfer function. The system of the present invention 1011 includes: [The present invention 1016] A method for treating a patient with acute myocardial infarction (AMI) using any of the systems of the present inventions 1001 to 1015. [The present invention 1017] measuring or calculating left ventricular systolic pressure (LVSP) in a left ventricle (LV) of a patient's heart, wherein a heart pump is implanted in the heart to perform mechanical unloading of blood from the LV to the aorta; controlling operation of the heart pump to maximize the mechanical unloading of the LV based on the measured or calculated LVSP; 1. A method for treating a patient with acute myocardial infarction (AMI), comprising: [The present invention 1018] The method of claim 1016, wherein the step of controlling the operation of the heart pump comprises controlling one or more of the pump speed and flow rate of the heart pump so that the LVSP in the LV is maintained at a target reference pressure. [The present invention 1019] 1017. The method of the present invention, wherein the target reference pressure is set to a ratio of the end-systolic pressure in normal ejection, said ratio being about 0.2 to about 0.4. [The present invention 1020] 1017. The method of claim 1017, wherein the target reference pressure is set to a ratio of the mean aortic pressure, said ratio being about 0.2 to about 0.4. [The present invention 1021] The method of the present invention 1017, wherein the target reference pressure is set to minimize the left ventricular pressure-volume area (PVA) by about 90% to about 97%. [The present invention 1022] The method of the present invention 1017, wherein the target reference pressure is set to minimize LV myocardial oxygen consumption (MVO2) by about 45% to about 48.5%.

[0016] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate exemplary embodiments and, together with the general description above and the detailed description below, serve to explain features of various embodiments. [Brief explanation of the drawings]

[0017] [Figure 1] Figure 1A shows the pressure-volume relationship of the LV during the cardiac cycle using an exemplary pressure-volume loop. Figure 1B shows an exemplary pressure-volume area (PVA) of the LV, representing the total mechanical work of the LV during a single contraction. [Figure 2] 1 shows the linear relationship between PVA and MVO2 during a single contraction (e.g., per beat). [Figure 3-1] 1 shows the effect of mechanical unloading of the LV by a cardiac pump on hemodynamics. [Figure 3-2] The effect of mechanical unloading of the LV by a cardiac pump on the pressure-volume loop, PVA, and LVSP is shown. [Figure 4] 1 is an illustration of an exemplary embodiment of a heart pump suitable for mechanical unloading of the LV. [Figure 5] FIG. 1 is a schematic diagram of one exemplary embodiment of a closed-feedback heart pump control system for controlling a heart pump to maximize mechanical unloading of the LV despite the presence of cardiovascular instability. [Figure 6] 6 illustrates an exemplary step response of the LVSP under the control of the feedback heart pump control system of FIG. 5. [Figure 7A] 6 illustrates exemplary performance of the feedback heart pump control system of FIG. 5 in response to changes in the target reference pressure value. [Figure 7B] 6 illustrates exemplary performance of the feedback heart pump control system of FIG. 5 in stabilizing a relevant index representative of MVO2 in the presence of large LV volume fluctuations. [Figure 8] 1 shows the relationship between PVA recruitment rate and LVSP rate for determining target baseline pressure. [Figure 9] FIG. 1 is a schematic diagram of one exemplary embodiment of an adaptive feedback heart pump control system. DETAILED DESCRIPTION OF THE INVENTION

[0018] Detailed Description Certain exemplary embodiments will now be described to provide a general 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 shown in the accompanying drawings are exemplary, non-limiting embodiments, and that the scope of the present disclosure is defined solely by the claims. Features shown or described in connection with one exemplary embodiment may be combined with features of other embodiments. Such modifications and variations are considered to be within the scope of the present disclosure. In this disclosure, similarly numbered components of various embodiments generally have similar characteristics if the components are of a similar nature and / or serve a similar purpose. Those skilled in the art will, in light of this disclosure, recognize various examples in which similarly numbered components between different drawings are homologous.

[0019] The present disclosure relates to various systems, devices, and methods for treating AMI patients using a cardiac pump controlled in a manner that maximizes LV mechanical unloading in the presence of cardiovascular instability, minimizes MVO2 and consequently infarct size, and prevents the subsequent development of heart failure.

[0020] Figure 1A shows the LV pressure-volume relationship during the cardiac cycle. Each of the pressure-volume loops 110 and 120 represents approximate LV pressure and LV volume measurements during one complete cardiac cycle. The cardiac cycle, or beat, can be divided into four basic phases: ventricular filling 110a, isovolumic contraction 110b, systolic ejection 110c, and isovolumic relaxation 110d. It is well established that end-systolic pressure is linearly correlated with end-systolic volume, shown as the end-systolic pressure-volume relationship (ESVPR, line 130). The ESPVR is virtually insensitive to changes in loading conditions, and its slope provides a good indication of ventricular contractility.

[0021] Figure 1B shows an exemplary pressure-volume area (PVA) of the LV, representing the total mechanical work of the LV during a single contraction. PVA is the specific surface area defined by the ESPVR and end-diastolic pressure-volume curve (EDPVR) and the systolic segment (SS) of the pressure-volume trajectory during contraction. Geometrically, in the pressure-volume plane, PVA is the sum of external work (EW) and potential energy (PE), i.e., PVA = PE + EW. As shown in Figure 1A, the PVA during the cardiac cycle, and therefore the total mechanical work of the ventricle, can be reduced by decreasing the LV end-systolic pressure (LVSP). For example, decreasing LVSP from LVSP 112 to LVSP 122 reduces PVA (e.g., from PVA 115 to PVA 125). As detailed herein, a heart pump can be used to reduce LVSP by reducing LV volume.

[0022] Figure 2 shows the linear relationship between PVA and MVO2 for a single contraction (e.g., per beat). It is well established that PVA is linearly correlated with MVO2 (line 210). Thus, a decrease in PVA (e.g., from PVA 220 to PVA 222) reduces MVO2 (e.g., from MVO2 230 to MVO2 232). It has been recognized that a decrease in MVO2 can reduce infarct size, i.e., the area of ​​necrotic tissue resulting from a heart attack.

[0023] Figures 3A–3F show the effects of mechanical unloading of the LV by a heart pump on hemodynamics, pressure-volume loops, PVA, and LVSP. For example, Figures 3A, 3B, and 3C show exemplary time series of changes in LV pressure (LVP) and aortic pressure (AP) for different levels of LV mechanical unloading. Figure 3D shows exemplary pressure-volume loops Lo (no mechanical unloading), Lp (partial mechanical unloading), and LMAX (maximum mechanical unloading) corresponding to each change in LVP. Figure 3A shows exemplary LV pressure (LVP) and aortic pressure (AP) without mechanical unloading by a heart pump. As shown in Figure 3B, partial mechanical unloading can reduce aortic pulse pressure, but the LV continues to eject, as evidenced by the pressure-volume loop Lp in Figure 3D. At maximum mechanical unloading, the LV no longer ejects, as indicated by the pressure-volume loop Lmax in Figure 3D, and the LV pressure LVP becomes lower than the aortic pressure AP, as shown in Figure 3C. FIG. 3E shows that maximum unloading can significantly reduce PVA (PVAMAX) and thus MV02. In AMI, maximum unloading is the state where infarct size is minimized. However, mechanical unloading can almost suddenly and sharply reduce LVSP even under relatively stable hemodynamic conditions, as shown in FIG. 3F for LVSPo and LVSP AMI in normal and AMI canine models. In AMI conditions, the heart and hemodynamic conditions are highly dynamic and subject to significant change, making it impractical, if not impossible, to maintain maximum unloading by manually controlling the heart pump. Thus, disclosed herein are embodiments of a closed-feedback control system for a heart pump that can be configured to maintain a predetermined target LVSP during mechanical unloading in the presence of hemodynamic instability inherent in AMI conditions.

[0024] 4A and 4B are illustrations of an exemplary embodiment of a heart pump 400 suitable for mechanical unloading of the LV. In the illustrated embodiment, the heart pump 400 can include an impeller pump 410, a pump motor 412, a blood inlet 414, and a blood outlet 416. In some embodiments, the pump 400 can be placed in a catheter 420 so that it can be inserted via standard catheterization procedures. For example, the heart pump 400 can be inserted into the femoral artery, into the ascending aorta 10, past the aortic valve 15, and into the left ventricle 20. A pressure sensor 430 can be placed in the catheter 420 to measure the LVSP during pump operation. In some embodiments, another pressure sensor 432 can also be placed in the catheter 420 to measure the aortic pressure. In some embodiments, the pressure sensor 432 used to measure the aortic pressure and / or differential pressure can also be used to calculate the LVSP during pump operation in the absence of the pressure sensor 430 in the left ventricle. The catheter 420 can also serve as a conduit to facilitate a wired connection from a remote control or console (eg, pump control 510 of FIG. 5) to the pump motor 412 and one or both of the pressure sensors 430, 432.

[0025] As shown, pump 400 can draw blood from the LV 20 through blood inlet 414 into impeller pump 410 and eject it through blood outlet 416 into the ascending aorta 10. The flow rate of heart pump 400 can be controlled based on the speed of pump motor 412. As described in more detail below, the speed of pump motor 412 can be controlled based on measurements obtained from LVSP sensor 430 and, optionally, aortic pressure sensor 432. In some embodiments, heart pump 400 can pump up to 5.0 liters per minute of blood from the LV to the aorta. In some embodiments, heart pump 400 can also pump at flow rates greater than or less than 5.0 liters per minute. Examples of heart pumps suitable for use with various embodiments can include the Impella® family of heart pumps, such as the Impella 5.0®, Impella LD®, Impella CP®, and Impella 2.5®, from Abiomed, Inc., based in Danvers, Massachusetts. Those skilled in the art will readily appreciate that other left ventricular assist devices or heart pumps may also be used.

[0026] Although various heart pumps can unload the LV, a pump that can generate sufficient cardiac output to support (i.e., perfuse) the entire body of an AMI patient would be useful. This is because, to minimize PVA, the LV must regularly cease ejection. This condition can be achieved when the mechanical unloading heart pump generates flow to perfuse the entire body. If the LV regularly ceases ejection, PVA, and therefore MVO2, can be minimized by controlling the heart pump flow. Various embodiments of the heart pump control system disclosed herein can be used with heart pumps that can generate cardiac output to support the entire body.

[0027] 5 is a schematic diagram of one exemplary embodiment of a closed-feedback heart pump control system 4500 for controlling a heart pump to maximize mechanical unloading of the left ventricle despite the presence of cardiovascular instability. In the illustrated embodiment, system 500 can include heart pump 400, pump controller 510, LVSP pressure sensor 430, and optionally, aortic pressure sensor 432. As described above with respect to FIG. 4B, heart pump 400 can be positioned within the heart to mechanically unload blood from the left ventricle to the aorta.

[0028] The pump controller 510 can 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 via 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.

[0029] In some embodiments, pressure sensor 430 and / or 432 can be configured to generate an output used by pump controller 510 to measure or calculate LVSP in the LV of the heart. For example, in some embodiments, pressure sensor 430 can be configured to measure LVSP and output it as a feedback signal to pump controller 510. Pump controller 510 can use the LVSP as feedback information to make speed adjustments to pump motor 412 so that the pump flow can maintain LVSP at or near a target base pressure that is lower than normal LVSP, and thus much lower than mean aortic pressure. In some embodiments, the target base pressure can be set by manual input to pump controller 510. In some embodiments, the target base pressure can be set to a calculated value obtained or determined by pump controller 510.

[0030] To automatically control the heart pump to minimize PVA and thus MVO2, the pump controller 510, sometimes referred to herein as a feedback controller, can be configured to control the speed, flow rate, or other operating characteristics of the heart pump to maintain LVSP at a low baseline pressure level despite significant changes in cardiac or hemodynamic conditions. This can be achieved when the open-loop gain of the feedback controller is large enough to stabilize LVSP fluctuations resulting from AMI-related significant cardiac and hemodynamic instability. In some embodiments, the heart pump feedback controller is stable and free of perturbations (or substantially free of perturbations) even in the presence of significant cardiac and hemodynamic instability. Control logic dictates that the higher the open-loop gain, the less stable the closed-loop feedback system. Thus, in some embodiments, the pump controller 510 can be configured to balance open-loop gain with system stability.

[0031] To develop a high open-loop gain feedback controller without sacrificing stability, an open-loop transfer function can be determined for the controlled plant. The plant can represent a heart augmented with a heart pump. For example, in some embodiments, the plant can model the dynamic change in LVSP in response to changes in pump speed of a heart pump used for mechanical unloading. For example, the plant can be defined as a single-input, single-output (SISO) system whose input is a pump speed control command (e.g., rpm) and whose output is LVSP (e.g., mmHg). In cardiovascular physiology, the transfer function of how changes in pump speed dynamically affect LVSP has not been studied. In some embodiments, the transfer function of the plant can also be determined using other inputs, such as the flow rate (e.g., milliliters per second) or other operating characteristics of the heart pump. In some embodiments, the transfer function of the plant can also be determined using other outputs, such as LV diastolic pressure, aortic pressure, or other properties of the cardiovascular system (e.g., heart) that can be measured or estimated using sensors (e.g., sensors 430, 432).

[0032] In some embodiments, computer modeling of the cardiovascular system can be used to estimate an approximate transfer function from pump speed to LVSP. In some embodiments, the transfer function can be approximated and reduced to the following second-order lag system: TIFF2025124788000004.tif13128In the formula, the four parameters are the gain K, the damping coefficient ζ, and the natural frequency f N and delay time L. The term j represents the imaginary unit (j 2 =-1). Because the second-order transfer function H(f) arises from the underlying anatomical structure of the cardiovascular system, the transfer function can be applied to many species with anatomical structures similar to the human cardiovascular system. The transfer function H(f) can also be used as a plant to model hearts augmented with cardiac pumps under diseased conditions, because such conditions are unlikely to involve major anatomical changes to the cardiovascular system.

[0033] In some embodiments, the four parameters of the plant transfer function H(f) are a gain K equal to about 0.013 mmHg / rpm, a damping coefficient ζ equal to about 1.9, a natural frequency f equal to about 0.41 Hz, and a N and a delay time L equal to about 0.03 seconds. As described in more detail below with respect to Figure 9, in some embodiments, the values ​​of one or more parameters of the plant transfer function H(f) can be varied in response to changes in AMI and volume loading conditions. Although the approximate values ​​of the parameters are based on animal studies and a canine model of AMI conditions, one skilled in the art will understand that these parameters can be adjusted to accommodate any variations associated with the human cardiovascular system.

[0034] Based on the identified plant transfer function H(f), the pump controller 510 can be configured to maintain the LVSP at a constant value despite changes in cardiac and hemodynamic conditions. For example, as shown in FIG. 5 , in some embodiments, the pump controller 510 can include a comparator 512 and a proportional-integral (PI) controller or a proportional-integral-derivative (PID) controller 514. The comparator 512 can be coupled to the pressure sensor 430 and configured to receive the measured LVSP output from the pressure sensor. The comparator 512 can be configured to compare a target reference pressure to the LVSP measured in the left ventricle and output a pressure difference or error signal e(t) to the PID controller 514.

[0035] The PID controller can be configured to implement the following equation: TIFF2025124788000005.tif10128 formula, K p is the proportional gain and K i is the integral gain, and K d is the differential gain, t is the time or instant, and τ is the integral variable that takes values ​​from time 0 to the present time t. The integral term can be configured to make the controller's degain infinity effectively equal to infinity. The equation u(t) is expressed in the Laplace domain as U(s)=Kp+Ki / s and K d It can be rewritten as s.

[0036] K p , K. i and K. d The value of K can be selected 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 step changes in pump speed or corresponding flow rate. For example, in some embodiments, K p , K. i and K. d The value of can be selected such 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 step response of the LVSP under closed-loop conditions can be less than about 10%, (ii) the time to reach a steady-state response of the LVSP can 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 can be zero on average. In some embodiments, the PID controller 514 can be implemented such that the feedback control system 500 is stable and can meet one or more of such constraints in the presence of changes in the open-loop gain of the plant (e.g., up to or greater than 16 times).

[0037] In some embodiments, based on the identified plant transfer function H(f), a minimal realization of the controller is achieved with a proportional gain K p , integral gain K equal to approximately 20 i and a proportional-integral (PI) controller with a derivative gain KJ equal to approximately 0. p and K. iThe combination of these values ​​for K can allow the system to maintain LVSP at a constant value in the presence of large instabilities in the AMI-induced cardiac and hemodynamic conditions, including changes in the open-loop gain of the plant (e.g., up to or greater than about 16-fold). In some embodiments, each gain parameter K p , K. i and K. d One or more of may be adjusted in response to changes in the design requirements and / or open-loop gain of the plant.

[0038] 6 illustrates an exemplary step response of LVSP under the control of the closed-feedback heart pump control system 500 of FIG. 5 using the above controller parameters. For example, as shown, the control system 500 can provide a step response 610 for LVSP that exhibits no overshoot and reaches steady state in approximately 20 seconds under AMI conditions. When the plant exhibits an open-loop gain that is four times larger than normal, the control system 500 can provide a step response 620 for LVSP that exhibits less than approximately 5% overshoot and reaches steady state in less than approximately 20 seconds. When the plant exhibits an open-loop gain that is one-quarter smaller than normal, the control system can provide a step response 630 for LVSP that exhibits no overshoot and reaches steady state in approximately 40 seconds.

[0039] Based on numerous animal studies conducted thoroughly under extreme AMI conditions, the open-loop gain of the plant was observed to vary within a factor of 4 to 1 / 4. In clinical applications, the open-loop gain associated with human patients should not vary by more than 16 times. A step response requiring approximately 20 to 40 seconds to reach steady state should be sufficient to avoid adverse effects on outcomes associated with ventricular unloading therapy. However, those skilled in the art will understand that the control system may be configured to reach steady state with other clinically relevant response times.

[0040] 7A and 7B illustrate exemplary performance of the closed-feedback heart pump control system of FIG. 5, which uses pump speed to control LVSP. For example, FIG. 7A illustrates the performance of the closed-feedback heart pump control system of FIG. 5, which uses pump speed to control LVSP. IN As the pressure is stepped through 40, 70 and 40 mmHg, the control system 500 adjusts the commanded pump speed S to produce an output LVSP that tracks the target pressure. out Figure 7A also shows that the output aortic pressure AP can be obtained by controlling the output LVSP. OUT and output LV volume LVV OUT Shows the change in

[0041] FIG. 7B illustrates the stabilization of relevant indices (e.g., LVSP and PVA) representing LV MVO2 consumption in the presence of large LV volume fluctuations (e.g., increases and decreases in left ventricular volume). Volume fluctuations are a hemodynamic instability inherent to AMI. As shown in FIG. 7B, despite large changes in volume (e.g., ±8 ml / kg), LVSP and PVA can remain substantially constant by using the feedback control system 500 of the present embodiment to control the pump speed of the heart pump (e.g., 400) to maintain a target LVSP. In comparison, using a fixed-speed heart pump allows LVSP and PVA to change significantly in response to large LV volume fluctuations.

[0042] In some embodiments, if a faster or more stable response is desired depending on the objective, one skilled in the art can adjust the gain parameter K of the PID controller 514. p , K. i and K. d It will be appreciated that one or more of the following may be adjusted. Accordingly, although specific gain parameter values ​​are disclosed herein for PID controllers, such values ​​are exemplary and not intended to be limiting.

[0043] As described above, the heart pump control system 500 of this embodiment can be configured to maintain LVSP at a target reference pressure determined to minimize LV MVO2. For example, as shown in FIGS. 1 and 2, MVO2 can be minimized by minimizing LV PVA. In theory, a zero PVA can minimize MVO2. However, maintaining PVA at zero (meaning an LVSP of zero mmHg) is very difficult to achieve safely and stably. This is because even a slight decrease in LVSP below zero can cause significant pump suction within the LV, which can damage the heart. Therefore, in some embodiments, the closed-feedback heart pump control system 500 of FIG. 5 can be configured to maintain LVSP at a target LVSP that provides approximately minimal MVO2 while still being safely and stably controllable by the feedback system. For example, in some embodiments, the target LVSP can be determined based on the relationship between the LVSP rate and the recruited PVA rate, as shown in FIGS. 8A and 8B.

[0044] FIG. 8A shows the relationship between LVSP fraction and LV volume fraction. As shown, pressure and volume are normalized to 1 at the end-systole of a normal ejection contraction. LVSP fraction "α" is the ratio of LVSP during unloading to end-systolic pressure during normal ejection, which defines the operating state of LV unloading. The lower the LVSP fraction α, the stronger the unloading. For a given LVSP fraction α, the LV volume fraction is also a because LV volume is normalized by end-systolic volume. LV end-diastolic volume is calculated by 1 / (1-β), where β is the LV ejection fraction, i.e., stroke volume divided by end-diastolic volume.

[0045] Recruited PVA is the PVA recruited by LV unloading under a working state of α. Residual PVA is the PVA remaining after unloading under a working state of α. The PVA recruitment rate is defined as the ratio of residual PVA to the sum of recruited and residual PVA, and indicates what proportion of total PVA is recruited by LV unloading. Mechanical unloading reduces the LVSP rate α, increasing recruited PVA and resulting in a decrease in LV residual PVA.

[0046] FIG. 8B shows the PVA recruitment fraction as a function of LVSP fraction "α" under various ejection fractions "β." As shown, the PVA recruitment fraction decreases with LVSP fraction α. ​​For example, at α=1 (i.e., LV volume fraction=1), PVA recruitment fractions 806, 804, and 802 are equal to 0.75, 0.57, and 0.33 for ejection fractions β of 0.6, 0.4, and 0.2, respectively. This means that an under-contracting LV may require greater unloading to reduce PVA. When α=0.4, PVA recruitment fractions 806′, 804′, and 802′ can be 0.9 or greater, regardless of the ejection fraction β. When α=0.2, PVA recruitment fractions 806″, 804″, and 802″ can be 0.97 or greater, regardless of the ejection fraction β.

[0047] Thus, in some embodiments, to minimize LV PVA by approximately 90% to 97%, the target LVSP can be set equal to the product of the end-systolic pressure during normal output and the LVSP fraction α (α is approximately 0.2 to approximately 0.4). End-systolic pressure during normal output is typically 70 to 110 mmHg. A target LVSP within such a range can be safely and stably achieved by mechanical unloading using a heart pump under the control of the feedback system 500 of this embodiment, as shown in FIG. 5. A reduction in PVA of approximately 90% to 97% can translate to a corresponding reduction in MVO2 of approximately 45% to 48.5%, respectively, assuming that 50% of MVO2 is PVA-independent. In the presence of significant noise in assessing infarct size, small differences in MVO2 are unlikely to affect infarct size. Such a reduction in MVO2 can achieve significant oxygen conservation, thereby reducing infarct size and subsequent heart failure.

[0048] In some embodiments, to minimize LV PVA by approximately 90% to 97%, the target LVSP can be set equal to the product of mean aortic pressure and LVSP fraction a, where a is approximately 0.2 to approximately 0.4. As noted above, a reduction in PVA of approximately 90% to 97% can correspond to a reduction in MVO2 of approximately 45 to approximately 48.5%, assuming that approximately 50% of MVO2 is PVA-independent. Such a reduction in MVO2 can achieve significant oxygen sparing, thereby reducing infarct size and subsequent heart failure.

[0049] In some embodiments, if the hemodynamic status of an AMI patient, including aortic pressure, is relatively stable, the target reference pressure (e.g., target LVSP) can be set to a fixed percentage of mean aortic pressure, such as, but not limited to, a percentage of about 0.2 to about 0.4. In some embodiments, the target reference pressure can be set to a fixed percentage of other hemodynamic parameters that can be measured or estimated. Once the target pressure is set, it is not changed until a clinical need arises. This simplifies setting a target pressure that is dependent on the patient's hemodynamic status.

[0050] 9 is a schematic diagram of one exemplary embodiment of an adaptive feedback heart pump control system 900. As shown, control system 900 can include a comparator 905, an adaptive pump controller 910, a heart pump actuator 920, a plant model 930, one or more sensors 940, a system identification module 950, and a controller design module 960. Except as described below, or as would be readily understood by one of ordinary skill in the art, control system 900 can be substantially similar to control system 500 described above with respect to FIGS. 4 and 5 . Accordingly, for the sake of brevity, a detailed description of its structure and functionality will not be provided herein. Control system 900 can include any one or more of the features of control system 500 described above.

[0051] In some embodiments, the adaptive feedback heart pump control system 900 can be used to control the heart pump to maintain a target LVSP or AP in AMI patients who may require the application of more complex mechanical unloading. For example, the application of more complex mechanical unloading may be expected in patients with right ventricular failure, life-threatening arrhythmias, and other mechanical circulatory systems. Therefore, a feedback heart pump control system configured to control a plant associated with a constant transfer function cannot guarantee that LVSP and PVA will remain constant. Therefore, using a system identification module 950 and a controller design module 960, the control system 900 can be adaptively configured to control the heart pump 920 based on continuous and / or periodic identification and updating of a plant model 930 representing a heart augmented with a heart pump (e.g., 400). In this manner, the adaptive pump controller 910 can be adaptively configured to minimize PVA and MOV2 in AMI patients under a wide variety of pathological conditions.

[0052] In some embodiments, system identification module 950 can be configured to periodically or continuously monitor and update the plant transfer function, and controller design module 960 can be configured to update one or more parameters of adaptive pump controller 910 in response to determined changes in the plant transfer function. For example, in some embodiments, system identification module 950 can update one or more of the parameters of the plant's second-order transfer function H(f), such as the gain K, the damping coefficient Λ, the natural frequency f, etc., in response to changes in the correlation between pump speed and LVSP. N and / or the delay time L. In some embodiments, the system identification module 940 can also be configured to model the plant using a transfer function other than the quadratic transfer function H(f). In some embodiments, the system identification module 950 can be configured to modify the plant transfer function based on sensor measurements of the LVSP in response to changes in pump speed.

[0053] Based on the determined change in the plant transfer function, controller design module 960 can adjust one or more parameters of adaptive pump controller 910. For example, if the adaptive pump controller is a PI or PID controller, controller design module 960 can adjust the proportional gain K associated with the controller. p , integral gain K i and the differential gain K d One or more of the following can be adjusted. p , K. i and K. d The adjustment value of can be selected to allow the measured LVSP to reach the target reference pressure with minimal overshoot and time delay in response to a corresponding adjustment in pump speed.

[0054] The various illustrative logic blocks, modules, circuits, and algorithmic operations described in connection with the aspects disclosed herein may be implemented as electronic hardware, computer software, or a combination of both. To clearly illustrate this interchangeability of hardware and software, the various illustrative components, blocks, modules, circuits, and operations are described above generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends on the particular application and design constraints imposed on the overall system. Those skilled in the art may implement the described functionality in different ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the claims.

[0055] The hardware used to implement the various example logic, logic blocks, modules, and circuits described in connection with aspects disclosed herein may be implemented with or performed by 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 components, or any combination thereof designed to perform the functions described herein. A general-purpose processor may be a microprocessor, but may alternatively be any conventional processor, controller, microcontroller, or state machine. A processor may also be implemented as a combination of receiver smart objects, e.g., a combination of a DSP and a microprocessor, two or more microprocessors, a combination of one or more microprocessors and a DSP core, or any other such configuration. Alternatively, some operations or methods may be performed by circuitry that is dedicated to a given function.

[0056] In one or more aspects, the functions described 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 or processor-readable storage medium. The operations of a method or algorithm disclosed herein may be embodied in a processor-executable software module or processor-executable instructions that may reside on a non-transitory computer-readable or processor-readable storage medium. A non-transitory computer-readable or processor-readable storage medium may be any storage medium that can be accessed by a computer or processor. By way of example, and without limitation, such non-transitory computer-readable or processor-readable storage medium may include 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. As used herein, disk and disc include compact discs (CDs), laser discs, optical discs, digital versatile discs (DVDs), floppy disks, and Blu-ray discs (disks typically reproduce data magnetically, while discs reproduce data optically using a laser). 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 code and / or instructions on a non-transitory processor-readable and / or computer-readable storage medium, which may be incorporated into a computer program product.

[0057] The above description of the disclosed embodiments is provided to enable any person skilled in the art to achieve or use the scope of the claims. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general 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 appended claims and the principles and novel features disclosed herein.

Claims

1. 1. A system for cardiac assistance including a heart pump, The heart pump comprises: a first portion configured to be placed within the patient's heart; a first sensor disposed within the first portion of the heart pump configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) within a left ventricle of the patient; a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the first sensor and to control operation of the heart pump to mechanically unload the left ventricle based on the measured or calculated LVSP; Including, the heart pump has a pump speed and a flow rate; the controller is configured to control one or more of the pump speed and the flow rate of the heart pump so that LVSP in the left ventricle is maintained at a target reference pressure; the control device is configured to set the target reference pressure to a ratio of end-systolic pressure during normal ejection; the end-systolic pressure is measured by the first sensor; the ratio is from about 0.2 to about 0.4; Systems for cardiac assistance.

2. 1. A system for cardiac assistance including a heart pump, The heart pump comprises: a first portion configured to be placed within the patient's heart; a first sensor disposed within the first portion of the heart pump configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) within a left ventricle of the patient; a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the first sensor and to control operation of the heart pump to mechanically unload the left ventricle based on the measured or calculated LVSP; Including, the heart pump has a pump speed and a flow rate; the controller is configured to control one or more of the pump speed and the flow rate of the heart pump so that LVSP in the left ventricle is maintained at a target reference pressure; the system further includes a second sensor disposed within a second portion of the heart pump configured to generate an output used to measure or calculate mean aortic pressure; the controller is configured to set the target reference pressure to a ratio of the mean aortic pressure; the ratio is from about 0.2 to about 0.4; Systems for cardiac assistance.

3. 1. A system for cardiac assistance including a heart pump, The heart pump comprises: a first portion configured to be placed within the patient's heart; a first sensor disposed within the first portion of the heart pump configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) within a left ventricle of the patient; a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the first sensor and to control operation of the heart pump to mechanically unload the left ventricle based on the measured or calculated LVSP; Including, the heart pump has a pump speed and a flow rate; the controller is configured to control one or more of the pump speed and the flow rate of the heart pump so that LVSP in the left ventricle is maintained at a target reference pressure; the controller is configured to set the target reference pressure to reduce a pressure-volume area (PVA) of the left ventricle; the controller estimates PVA based on the measured or calculated LVSP and one or more measurements of left ventricular volume. Systems for cardiac assistance.

4. 4. The system of claim 3, wherein the control device is configured to set the target baseline pressure to reduce left ventricular PVA by about 90% to about 97%.

5. The control device adjusts the target reference pressure based on the myocardial oxygen consumption (MVO 2 ), and the control device is configured to set the MVO 2 Based on the linear relationship between MVO and PVA 2 The system of claim 3, wherein the system estimates:

6. The control device sets the target reference pressure to the left ventricular MVO 2 6. The system of claim 5, configured to set the power consumption to reduce by about 45% to about 48.5%.

7. 1. A system for cardiac assistance including a heart pump, The heart pump comprises: a first portion configured to be placed within the patient's heart; a first sensor disposed within the first portion of the heart pump configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) within a left ventricle of the patient; a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the first sensor and to control operation of the heart pump to mechanically unload the left ventricle based on the measured or calculated LVSP; Including, the heart pump has a pump speed and a flow rate; the controller is configured to control one or more of the pump speed and the flow rate of the heart pump so that LVSP in the left ventricle is maintained at a target reference pressure; the controller is configured to control one or more of the pump speed and the flow rate of the heart pump to maintain the LVSP at the target reference pressure based on a plant transfer function that models changes in LVSP in response to changes in pump speed; the system further includes a non-transitory computer-readable or processor-readable storage medium configured to store the plant transfer function as one or more instructions or code; The plant transfer function is a second-order delay system. Systems for cardiac assistance.

8. If the plant transfer function is where K is the gain, ζ is the damping coefficient, and f N is the natural frequency and L is the time lag) 8. The system of claim 7, wherein the system is a second-order lag system having a time lag defined as:

9. The gain K is approximately equal to 0.013 mmHg / rpm, the damping coefficient ζ is approximately equal to 1.9, and the natural frequency f N 9. The system of claim 8, wherein the time lag L is equal to about 0.03 seconds.

10. 10. The system of claim 9, wherein the controller is configured to control one or more of a pump speed and a flow rate of the heart pump so that the LVSP reaches the target reference pressure in less than a clinically determined response time and with less than 10% overshoot of the target reference pressure.

11. 10. The system of claim 9, wherein the controller is configured to control one or more of a pump speed and a flow rate of the heart pump to maintain the LVSP at the target reference pressure when the open-loop gain of the plant transfer function changes by a factor of 16 or less.

12. The control device A proportional-integral controller consisting of a proportional gain equal to approximately 40, an integral gain equal to approximately 20, and a derivative gain equal to approximately 0.

10. The system of claim 9, comprising:

13. The control device an adaptive control mechanism configured to update a plant transfer function and reconfigure the controller to control one or more of a pump speed and a flow rate of the heart pump in response to changes in the plant transfer function.

10. The system of claim 9, comprising:

14. 1. A system for cardiac assistance including a heart pump, The heart pump comprises: a first portion configured to be placed within the patient's heart; a first sensor disposed within the first portion of the heart pump configured to generate an output used to measure or calculate left ventricular systolic pressure (LVSP) within a left ventricle of the patient; a controller coupled to the heart pump and configured to measure or calculate the LVSP based on the output of the first sensor and to control operation of the heart pump to mechanically unload the left ventricle based on the measured or calculated LVSP; Including, the heart pump has a pump speed and a flow rate; the controller is configured to control one or more of the pump speed and the flow rate of the heart pump so that LVSP in the left ventricle is maintained at a target reference pressure; The system further includes a storage medium configured to store the plant transfer function; the controller is configured to control the heart pump to maintain the LVSP at a target reference pressure based on the plant transfer function that models changes in LVSP in response to changes in pump speed; The plant transfer function is a second-order delay system. Systems for cardiac assistance.

15. 15. The system of claim 14, wherein the delay is based on a ratio between an exponential function and a quadratic function.

16. 16. The system of claim 15, wherein the quadratic function includes a damping coefficient ζ that is the coefficient of a first-order component of the quadratic function.

Images