System and method for controlling a cardiac pump to minimize myocardial oxygen consumption

Abstract

This disclosure relates to various systems, devices, and methods for treating patients with acute myocardial infarction (AMI) using a heart pump that is controlled in a manner that maximizes mechanical unloading of the left ventricle and minimizes myocardial oxygen consumption (MVO2) and, accordingly, infarct size in the presence of cardiovascular instability to prevent the development of subsequent heart failure. In a closed feedback system, the system can include a sensor configured to generate an output for measuring or calculating a left ventricular systolic pressure (LSVP) within a left ventricle of the heart and a controller coupled to the heart pump. The controller can be configured to measure or calculate the LVSP based on the output of the sensor and control the operation of the heart pump based on the measured or calculated LVSP to maximize mechanical unloading of the left ventricle.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of U.S. Patent Application No. 16 / 050,542, filed on July 31, 2018, entitled “Systems and Methods for Controlling a Heart Pump to Minimize Myocardial Oxygen Consumption,” the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to systems for controlling a cardiac pump and related methods for treating patients suffering from acute myocardial infarction (AMI), and in particular to a closed feedback control system for controlling the operation of a cardiac pump to maximize mechanical unloading of the left ventricle (LV) and to minimize myocardial oxygen consumption (MVO2) and, therefore, infarct size to prevent the development of long-term heart failure during treatment of AMI patients. Background Art

[0004] An AMI, commonly called a heart attack, can be a life-threatening condition that occurs when blood flow to the heart muscle is suddenly cut off, causing tissue damage. Dead tissue, or infarction, can form in the heart due to insufficient blood supply to the affected area. An AMI is usually the result of a blockage in one or more coronary arteries. The coronary arteries carry oxygen-rich blood to the heart muscle. When these arteries become blocked or narrowed, blood flow to the heart can be significantly reduced or completely stopped.

[0005] AMI may require immediate medical treatment to restore blood flow through the blocked artery, sometimes also referred to as reperfusion therapy. For example, reperfusion therapy may include surgery to remove or bypass 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 but not limited to thrombolytics, fibrinolytics, beta-blockers, and nitroglycerin.

[0006] In some AMI patients, a heart pump can be used to stabilize hemodynamics and make it possible to perform safe and effective reperfusion therapy to save the affected ischemic myocardium. For example, recent clinical trials as well as basic research have shown that LV assist 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 thereby reduce MVO2. It has been observed that a reduction in MVO2 can reduce infarct size, that is, the area of ​​dead tissue caused by a heart attack. The degree of reduction in infarct size generally corresponds to a reduction in MVO2.

[0007] Although mechanical unloading of the LV has such a beneficial effect on AMI, its clinical application has not yet been established. In patients with chronic heart failure, manual control of the LVAD flow rate (e.g., liters per minute) can achieve stable hemodynamics. However, in AMI patients, the cardiac and hemodynamic conditions are inherently unstable because AMI can significantly change the heart's contractility, vascular resistance, blood pressure, pressure volume, heart rate, and / or the activity of the sympathetic and parasympathetic autonomic nervous systems within seconds, minutes, or hours. It is known that these variabilities can significantly affect hemodynamics. Therapeutic interventions such as drug therapy and reperfusion may further cause complex dynamic adjustments of these variables and lead to complex hemodynamics.

[0008] In the presence of such cardiovascular instability in AMI, it may be difficult, if not impractical, to avoid mechanically unloading the LV too much or too little, even with frequent monitoring or continuous manual precision adjustment of LVAD flow. Mechanically unloading the LV at a flow rate slightly 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 slightly less than the fill rate increases LV volume and MVO2, and makes it difficult to reduce the infarct size of the LV. Therefore, manually controlling the heart pump to optimally unload the LV is impractical, ineffective, and potentially life-threatening.

[0009] Therefore, there is a need for improved systems and related methods for treating AMI patients using a heart pump that is controlled in a manner that optimizes mechanical unloading of the LV, regardless of the presence of cardiovascular instability, thereby optimally reducing MVO2 and infarct size. Summary of the invention

[0010] The present disclosure relates to various systems, devices and methods for treating AMI patients using a heart pump that is controlled in a manner that maximizes mechanical unloading of the LV in the presence of cardiovascular instability and minimizes MVO2 and, accordingly, infarct size to prevent the subsequent development of heart failure.

[0011] In an exemplary embodiment of a system for controlling a heart pump, the system includes a sensor and a controller coupled to the heart pump, the sensor being configured to generate an output for measuring or calculating left ventricular systolic pressure (LSVP) within the left ventricle of the heart, and the controller being configured to measure or calculate the LVSP based on the output of the sensor, and to control the operation of the heart pump based on the measured or calculated LVSP to maximize mechanical unloading of the left ventricle.

[0012] In some embodiments, the controller can be configured to control one or more of the pump rate 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 fraction of the end-systolic pressure in a normal ejecting beat, the fraction being between about 0.2 and about 0.4. The target reference pressure can be set to a fraction of the mean aortic pressure, the fraction being between about 0.2 and 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%.

[0013] 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 a target reference pressure based on a plant transfer function that models changes in the LVSP in response to changes in the pump speed. For example, the plant transfer function can be a second-order delay system with time lag, defined as:

[0014]

[0015] Where K is the gain, ζ is the damping factor, 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 factor ζ can be equal to about 1.9, and the natural frequency f N can be equal to approximately 0.41 Hz, and the time lag L can be equal to approximately 0.03 seconds.

[0016] 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 predetermined response time and with an overshoot of less than 10% of the target reference pressure. When the open-loop gain of the plant transfer function changes by a factor of 16 or less, 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. In some embodiments, the controller can 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 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.

[0017] In one exemplary embodiment of a method for treating an acute myocardial infarction (AMI) patient, the method includes measuring or calculating the LSVP within the LV of the patient's heart and controlling the operation of a heart pump based on the measured or calculated LVSP to maximize mechanical unloading of the LV. The heart pump is implanted in the heart to mechanically unload blood from the LV to the aorta.

[0018] In some embodiments, controlling the operation of the heart pump may include controlling one or more of a pumping rate and a flow rate of the heart pump so that the LVSP within the left ventricle is maintained at a target reference pressure. The target reference pressure may be set to a fraction of the end-systolic pressure in a normal ejection stroke, 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, the fraction being 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 minimize the myocardial oxygen consumption (MVO2) of the left ventricle by about 45% to about 48.5%. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The accompanying drawings, which are incorporated herein and constitute a 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 various embodiments:

[0020] Figure 1A The pressure-volume relationship of the LV during the cardiac cycle is illustrated using exemplary pressure-volume loops.

[0021] Figure 1B An exemplary pressure-volume area (PVA) of the LV is illustrated, and the total mechanical work of the LV in a single contraction is represented.

[0022] Figure 2A linear relationship between PVA and MVO2 within a single contraction (eg, each beat) is demonstrated.

[0023] Figures 3A-3F The effects of mechanical unloading of the LV by the cardiac pump on hemodynamics, pressure-volume loop, PVA, and LVSP are demonstrated.

[0024] Figure 4A and 4B is a schematic diagram of an exemplary embodiment of a heart pump suitable for mechanical unloading of the LV.

[0025] Figure 5 is a schematic diagram of an exemplary embodiment of a closed feedback heart pump control system for controlling a heart pump to maximize mechanical unloading of the LV regardless of the presence of cardiovascular instability.

[0026] Figure 6 Explained in Figure 5 Exemplary step response of the LVSP under control of a feedback heart pump control system.

[0027] Fig. 7A The response to the change of the target reference pressure value is shown. Figure 5 Exemplary performance of a feedback heart pump control system.

[0028] Figure 7B This illustrates the presence of severe LV volume disturbances. Figure 5 Exemplary performance of a feedback cardiac pump control system in stabilizing a relevant metric representing MVO2 consumption.

[0029] Fig. 8A and 8B The relationship between the PVA recruitment fraction and the fractional LVSP is illustrated to determine the target reference pressure.

[0030] Fig. 9 is a schematic diagram of an exemplary embodiment of an adaptive feedback heart pump control system. DETAILED DESCRIPTION

[0031] Certain exemplary embodiments will now be described to provide an overall understanding of the principles of 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. It will be appreciated by those skilled in the art that the systems, devices and methods specifically described herein and illustrated in the accompanying drawings are non-restrictive exemplary embodiments, and the scope of the present disclosure is limited only by the claims. The features illustrated or described in conjunction with an exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present disclosure. In the present disclosure, when similarly numbered parts of various embodiments have similar properties and / or are used for similar purposes, they generally have similar features. According to the present disclosure, it will be appreciated by those skilled in the art that various examples are similar in which similarly numbered parts in multiple figures are similar.

[0032] The present disclosure relates to various systems, devices and methods for treating AMI patients using a heart pump that is controlled in a manner that maximizes LV mechanical unloading and minimizes MVO2 and corresponding infarct size in the presence of cardiovascular instability to prevent the subsequent development of heart failure.

[0033] Figure 1A 1 illustrates the pressure-volume relationship of the LV during the cardiac cycle. Each of the pressure-volume loops 110 and 120 represents an approximate LV pressure and LV volume measurement 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 110d. 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). The ESPVR is essentially insensitive to changes in loading conditions and its slope is a good representation of the contractility of the ventricle.

[0034] Figure 1B An exemplary pressure-volume area (PVA) of the LV is illustrated and represents the total mechanical work of the LV in a single contraction. The PVA is a specific area bounded by the ESPVR and the end-diastolic pressure-volume curve (EDPVR) and the systolic segment (SS) of the pressure-volume trajectory in contraction. Geometrically in the pressure-volume plane, the PVA is the sum of the external work (EW) and the potential energy (PE), i.e., PVA = PE + EW. Figure 1AAs shown, the PVA of the cardiac cycle can be reduced by reducing the LV end-systolic pressure (LVSP), thereby reducing the total mechanical work of the ventricle. For example, reducing the LVSP from LVSP 112 to LVSP 122 will reduce the PVA (e.g., PVA 115 to PVA 125). As discussed herein, a heart pump can be used to reduce the LVSP by reducing the LV volume.

[0035] Figure 2 The linear relationship between PVA and MVO2 in a single contraction (e.g., each beat) is illustrated. As is well known, PVA is linearly related to MVO2 (line 210). Thus, a decrease in PVA (e.g., PVA 220 to PVA 222) reduces MVO2 (e.g., MVO2 230 to MVO2 232). It has been observed that a decrease in MVO2 can reduce infarct size, or the area of ​​dead tissue caused by a heart attack.

[0036] Figures 3A-3F The effects of LV mechanical unloading by the cardiac pump on hemodynamics, pressure-volume loop, PVA, and LVSP are described. For example, Figure 3A , 3B 3C illustrate exemplary changes in LV pressure (LVP) and aortic pressure (AP) over time series for different levels of mechanical unloading of the LV. Figure 3D Exemplary pressure-volume loops Lo (no mechanical unloading), Lp (partial mechanical unloading), and LMAX (maximum mechanical unloading) corresponding to various changes in LVP are illustrated. Figure 3A Exemplary LV pressure (LVP) and aortic pressure (AP) without mechanical unloading by the heart pump are illustrated. Figure 3B As shown, partial mechanical unloading can reduce aortic pulse pressure, but Figure 3D As shown by the pressure-volume loop Lp in the figure, the LV is still pumping blood. When the mechanical unloading reaches the maximum, the LV no longer pumps blood, as shown in Figure 3D As shown in the pressure-volume loop Lmax in , and the LV pressure LVP is lower than the aortic pressure AP, as shown in Figure 3C shown. Figure 3E Showing maximal unloading makes the PVA (PVAMAX) and therefore MVO2 very small. In AMI, maximal unloading is the condition in which the infarct size becomes minimal. However, if Figure 3FAs shown in the normal and AMI canine models of LVSPo and LVSPAMI in Figure 1, mechanical unloading can almost produce an abrupt and dramatic drop in LVSP even under relatively stable hemodynamic conditions. In the AMI condition, it may be impractical, if not impossible, to maintain a maximum amount of unloading by manually controlling the heart pump because the cardiac and hemodynamic conditions can be extremely dynamic and may vary widely. Therefore, embodiments of a closed feedback control system for a heart pump are disclosed herein that can be configured to maintain a predetermined target LVSP during mechanical unloading in the presence of the hemodynamic instability inherent to the AMI condition.

[0037] Figure 4A and 4B 4 is a schematic diagram of an exemplary embodiment of a heart 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 a catheter 420 so that the heart pump 400 can be inserted through a standard catheter insertion procedure. For example, the heart pump 400 can 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 can be disposed in the catheter 420 to measure the LVSP during operation of the pump. In some embodiments, another pressure sensor 432 can be disposed in the catheter 420 to measure aortic pressure. In some embodiments, in the absence of a pressure sensor 430 in the left ventricle, a pressure sensor 432 for measuring aortic pressure and / or pressure differential can be used to calculate the LVSP during operation of the pump. The catheter 420 can also be used as a conduit to facilitate control from a remote control or console (e.g., Figure 5 A wired connection is provided to the pump controller 510) to the pump motor 412 and to the pressure sensors 430, 432, or both.

[0038] As shown, the pump 400 can pull blood from the LV 20 into the impeller pump 410 through the blood inlet 414 and discharge the blood into the ascending aorta 10 through the blood outlet 416. The flow rate of the heart pump 400 can be controlled based on the speed of the pump motor 412, which can be controlled based on measurements obtained from the LVSP sensor 430 and, optionally, the aortic pressure sensor 432, as discussed in more detail below. In some embodiments, the heart pump 400 can pump up to 5.0 liters of blood per minute from the LV to the aorta. In some embodiments, the heart pump 400 can pump at a flow rate greater than or less than 5.0 liters per minute. Examples of heart pumps suitable for use in various embodiments can include the 1000-1000 liters per minute pumps from Abiomed, Inc., headquartered in Danvers, Massachusetts. Heart pump family, including but not limited to Impella Impella Impella and Impella One of ordinary skill will readily appreciate that other left ventricular assist devices or heart pumps may be used.

[0039] Although various heart 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 in order to minimize PVA, the LV needs to stop ejecting blood periodically. This condition can be achieved when the heart pump used for mechanical unloading produces flow to perfuse the entire body. Once the LV stops ejecting blood periodically, PVA and MVO2 can be minimized by controlling the heart pump flow. Various embodiments of the heart pump control system disclosed herein can be used with a heart pump that is capable of producing a cardiac output to support the entire body.

[0040] Figure 5 is a schematic diagram of an exemplary embodiment of a closed feedback heart pump control system 4500 for controlling a heart pump to maximize mechanical unloading of the left ventricle regardless of the presence of cardiovascular instability. In the illustrated embodiment, the system 500 may include a heart pump 400, a pump controller 510, a LVSP pressure sensor 430, and optionally an aortic pressure sensor 432. As described above with respect to Figure 4B As discussed, the heart pump 400 may be placed within the heart to mechanically unload blood from the left ventricle into the aorta.

[0041] The pump controller 510 can be configured to control the flow rate of the pump 410 by adjusting the speed (e.g., rotations 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 the target pressure.

[0042] In some embodiments, the pressure sensors 430 and / or 432 can be configured to generate an output that is used by the pump controller 510 to measure or calculate the LVSP within the LV of the heart. For example, in some embodiments, the pressure sensor 430 can be configured to measure the LSVP and output it as a feedback signal to the pump controller 510. The pump controller 510 can use the LVSP as feedback information to make speed adjustments to the pump motor 412 so that the flow rate of the pump can maintain the LVSP at or near a target reference pressure that is less than a normal LVSP and thus much lower than the mean aortic pressure. In some embodiments, the target reference pressure can be set to the pump controller 510 by manual input. In some embodiments, the target reference pressure can be set to a calculated value obtained or determined by the pump controller 510.

[0043] In order to automatically control the heart pump to minimize PVA and thereby minimize 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 keep the LVSP at a low reference pressure level, regardless of 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 caused by severe cardiac and hemodynamic instabilities associated with AMI. In some embodiments, the feedback controller of the heart pump is stable and has no oscillations (or virtually no oscillations) in the presence of severe cardiac and hemodynamic instabilities. Control theory shows that the higher the open-loop gain, the lower the stability of the closed-loop feedback system. Therefore, in some embodiments, the pump controller 510 can be configured to balance the open-loop gain with system stability.

[0044] In order to develop a high open-loop gain feedback controller without compromising stability, an open-loop transfer function can be determined for the controlled object to be controlled. The controlled object can represent a heart enhanced with a heart pump. For example, in some embodiments, the controlled object can model the dynamic changes of the LVSP in response to changes in the pump speed of a heart pump used for mechanical unloading. For example, the object can 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 the LVSP (e.g., mmHg). In cardiovascular physiology, the transfer function of how pump speed changes dynamically affect the LVSP has never been studied. In some embodiments, other inputs can 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 can be used to define the transfer function of the controlled object, 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).

[0045] In some embodiments, a computational model of the cardiovascular system can be used to estimate an approximate transfer function from pump rate to LVSP. In some embodiments, the transfer function can be approximated and simplified as a second-order system with delays, such as:

[0046]

[0047] The four parameters are gain K, damping factor ζ, natural frequency f N and delay time L. The term j represents the imaginary part, where j 2 = -1. Since the second-order transfer function H(f) is derived 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) can also be used as a controlled object to model a heart with cardiac pump augmentation in a diseased state, since such a condition is unlikely to involve severe anatomical changes in the cardiovascular system.

[0048] In some embodiments, the four parameters of the object transfer function H(f) may include a gain K equal to or approximately 0.013 mmHg / rpm, a damping factor ζ equal to or approximately 1.9, a natural frequency f equal to or approximately 0.41 Hz, and a N , a delay time L equal to or approximately 0.03 seconds. Fig. 9 As discussed, in some embodiments, the values ​​of one or more parameters of the plant transfer function H(f) can be changed in response to changes in AMI and volume loading conditions. Although the approximate values ​​of the aforementioned parameters are based on animal experiments and canine models under AMI conditions, 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.

[0049] Based on the identified plant transfer function H(f), the pump controller 510 can be configured to maintain the LVSP at a constant value regardless of changes in cardiac and hemodynamic conditions. Figure 5 As shown, 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 difference or error signal e(t) to the PID controller 514.

[0050] The PID controller can be configured to implement the following equation:

[0051]

[0052] Where K p is the proportional gain, K i is the integral gain, K d is the derivative gain, t is the time or instantaneous time, and τ is the integral variable whose value runs from time 0 to the current time t. The integral term can be configured to make the controller gain infinite, effectively equal to infinity. The equation u(t) can be rewritten in the Laplace domain as U(s) = K p +K i / s and K d s.

[0053] You can choose K p , K i and K d The system 500 is tuned by using a value of K so that the time or frequency response of the LVSP of the closed-loop system can be optimized with respect to a step change in pump speed or corresponding flow rate. For example, in some embodiments, K can be selected to p , K i and K d The value of LVSP can be set so that in response to the corresponding adjustment of the pump speed, the measured LVSP can reach the target reference pressure with minimal overshoot and time delay. For example, in some embodiments, (i) the overshoot of the LVSP step response under closed-loop conditions can be less than about 10%, (ii) the time to reach the LVSP steady-state response 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 average to zero. In some embodiments, the PID controller 514 can be implemented so that the feedback control system 500 is stable and can meet one or more of these constraints when the open-loop gain of the controlled object changes (e.g., to a maximum) by as much as or more than 16 times.

[0054] In some embodiments, based on the identified transfer function of the controlled plant H(f), a minimum implementation of the controller may be a controller having a proportional gain K equal to or approximately 40. p , an integral gain K equal to or approximately 20 i A proportional-integral (PI) controller with a derivative gain KJ equal to or approximately 0. Gain K p and K i The combination of these values ​​of can enable the system to maintain the LVSP at a constant value in the presence of severe instabilities in AMI-induced cardiac and hemodynamic conditions (including changes in the open-loop gain of the controlled subject, such as up to or exceeding equal to or about 16 times). In some embodiments, each gain parameter K p , K i and K dOne or more of can be adjusted in response to changes in design requirements and / or the open-loop gain of the object.

[0055] Figure 6 This shows how to use the above controller parameters in Figure 5 6. Example step responses of the LVSP under control of the closed feedback heart pump control system 500. For example, as shown, the control system 500 can provide a step response 610 for the LVSP that exhibits no overshoot and reaches steady state in about 20 seconds under AMI conditions. 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 for the LVSP that exhibits less than about 5% overshoot and reaches steady state in about 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 can provide a step response 630 for the LVSP that exhibits no overshoot and reaches steady state in about 40 seconds.

[0056] Based on extensive animal experiments conducted in extreme AMI conditions, it was observed that the open loop gain of the controlled object varied within a range of 4 to 1 / 4 times. In clinical applications, the open loop gain variation associated with human patients should not exceed 16 times. A step response that takes about 20 seconds to 40 seconds to reach steady state 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 can be configured to reach steady state at other clinically relevant response times.

[0057] Fig. 7A and 7B Describes the use of pump speed to control LVSP Figure 5 Example performance of a closed feedback heart pump control system. For example, Fig. 7A It shows that when the target reference pressure LVSP is input IN When changing stepwise from 40, 70, and 40 mmHg, the control system 500 can adjust the commanded pump speed S to provide an output LVSP that follows the target pressure. OUT . Fig. 7A The output aortic pressure AP associated with the controlled output LVSP is also shown. OUT and LV volume OUT changes.

[0058] Figure 7B The stability of related indices representing LV MVO2 consumption (e.g., LVSP and PVA) in the presence of severe volume perturbations (e.g., increases or decreases in left ventricular volume) is demonstrated. Volume perturbations are inherent to the hemodynamic instability of AMI. Figure 7BAs shown, despite severe changes in volume (e.g., ±8 ml / kg), the LVSP and PVA can be kept substantially constant to maintain a target LVSP by controlling the pumping speed of a heart pump (e.g., 400) using an embodiment feedback control system 500. In contrast, when a fixed speed heart pump is used, the LVSP and PVA can vary significantly in response to severe volume disturbances of the LV.

[0059] In some embodiments, where a faster or more stable response is desired, one of ordinary skill in the art will recognize that the gain parameter K of the PID controller 514 may be p , K i and K d One or more of can be adjusted. Therefore, although specific gain parameter values ​​for the PID controller are disclosed herein, these values ​​are exemplary and not limiting.

[0060] As described above, the heart pump control system 500 of the embodiment can be configured to maintain the LVSP at a target reference pressure determined to minimize the MVO2 of the LV. For example, as shown in Figures 1 and 2, the MVO2 can be minimized by minimizing the PVA of the LV. In theory, a PVA of zero can minimize the MVO2. However, maintaining the PVA at zero (which means that the LVSP is zero mmHg) is difficult to achieve safely and stably because even a small decrease in the LVSP below zero can cause the pump to generate severe suction in the LV that is damaging to the heart. Therefore, in some embodiments, Figure 5 The closed feedback heart pump control system 500 can be configured to maintain the LVSP at a target LVSP that provides approximately the minimum MVO2 and can still be safely and stably controlled by the feedback system. For example, in some embodiments, Fig. 8A and 8B As shown, the target LVSP can be determined based on the relationship between the fractional LVSP and the recruited fractional PVA.

[0061] Fig. 8A The relationship between fractional LVSP and fractional LV volume is illustrated. As shown, in normal ejection contraction, pressure and volume are normalized to unity at the end of systole. The fractional LVSP "α" is the ratio of the LVSP during unloading to the end-systolic pressure during normal ejection, which defines the operating condition of the LV unloading. The lower the fractional LVSPα, the greater the unloading. For a given fractional LVSPα, the fractional LV volume also becomes the factor because the LV volume has been normalized by the end-systolic volume. The LV end-diastolic volume is given by 1 / (1-β), where β is the LV ejection fraction, which is the stroke volume divided by the end-diastolic volume.

[0062] Recruited PVA is the PVA recruited by LV unloading under alpha operating conditions. Residual PVA is the PVA that remains by unloading under alpha operating conditions. Fractional PVA recruitment is defined by the ratio of residual PVA to the sum of recruited and residual PVA, which represents the percentage of total PVA recruited by LV unloading. Mechanical unloading reduces fractional LVSPα, increases recruited PVA, and results in a decrease in residual PVA in the LV.

[0063] Figure 8B The function of fractional PVA recruitment and fractional LVSP "α" at various ejection fractions "β" is illustrated. As shown, fractional PVA recruitment decreases with fractional LVSP α. For example, at α=1 (i.e., where fractional LV volume=1), for ejection fractions β of 0.6, 0.4, and 0.2, fractional PVA recruitment 806, 804, and 802 are equal to 0.75, 0.57, and 0.33, respectively. This means that a poorly contracted LV may require greater unloading to reduce PVA. For α=0.4, fractional PVA recruitment 806', 804', 802' can be greater than or equal to 0.9, regardless of ejection fraction β. For α=0.2, fractional PVA recruitment 806", 804", 802" can be greater than or equal to 0.97, regardless of ejection fraction β.

[0064] Thus, in some embodiments, the target LVSP can be set equal to the product of the end-systolic pressure during a normal ejection pulse and the fractional LVSPα, where the value of α is between about 0.2 and about 0.4, to minimize the PVA of the LV by about 90% to 97%. During a normal ejection pulse, the end-systolic pressure is typically between 70 and 110 mmHg. Figure 5 Embodiments of the feedback system 500 can safely and consistently achieve a target LVSP within this range by mechanically unloading the heart pump under control. Assuming that an MVO2 of 50% is independent of PVA, a reduction in PVA of approximately 90% to 97% can translate into a corresponding reduction in MVO2 of approximately 45% to 48.5%, respectively. In the presence of significant noise in assessing infarct size, small differences in MVO2 are unlikely to affect infarct size. Such reductions in MVO2 can achieve important oxygen savings and thereby reduce infarct size and subsequent heart failure.

[0065] In some embodiments, the target LVSP can be set equal to the product of the mean aortic pressure and the fractional LVSPα, where the value of α is between about 0.2 and about 0.4, to minimize the PVA of the LV by about 90% to about 97%. As described above, assuming that an MVO2 of about 50% is independent of PVA, a reduction in PVA of about 90% to 97% can correspond to a reduction in MVO2 of about 45% to about 48.5%. Such a reduction in MVO2 can achieve important oxygen conservation and thereby reduce infarct size and subsequent heart failure.

[0066] In some embodiments, where the hemodynamics of an AMI patient are relatively stable (including aortic pressure), a target reference pressure (e.g., target LSVP) can be set to a fixed fraction of the mean aortic pressure, such as, but not limited to, a fraction between about 0.2 and about 0.4. In some embodiments, the target reference pressure can be set to a fixed fraction of other hemodynamic parameters that can be measured or estimated. Once the target pressure is set, it is not changed until clinical necessity arises. This simplifies setting the target pressure based on the patient's hemodynamic condition.

[0067] Fig. 9 is a schematic diagram of an exemplary embodiment of an adaptive feedback heart pump control system 900. As shown, the control system 900 may include a comparator 905, an adaptive pump controller 910, a heart pump actuator 920, a controlled 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 will be readily understood by one of ordinary skill in the art, the control system 900 may be substantially similar to the control system 500 described above with respect to FIGS. 4 and 5. For the sake of brevity, a detailed description of its structure and function is omitted herein. The control system 900 may include any one or more features of the control system 500 described above.

[0068] 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 more complex mechanical unloading applications. For example, in patients with right ventricular failure, life-threatening heart rhythms, and other mechanical circulatory devices, more complex mechanical unloading applications may be desired. Therefore, a feedback heart pump control system configured to control a plant associated with a fixed transfer function may not be able to ensure that the LVSP and PVA are constant. Therefore, the system identification module 950 and the controller design module 960 can be used to adaptively configure the control system 900 to control the heart pump 920 based on continuous and / or periodic identification and updating of a plant model 930 representing a heart enhanced with a heart pump (e.g., 400). In this way, the adaptive pump controller 910 can be adaptively configured to minimize PVA and MVO2 in patients with AMI under a variety of pathological conditions.

[0069] In some embodiments, the system identification module 950 can be configured to periodically or continuously monitor and update the plant transfer function, and the controller design module 960 can be configured to update one or more parameters of the adaptive pump controller 910 in response to the determined changes in the plant transfer function. For example, in some embodiments, the system identification module 950 can be configured to adjust one or more parameters of the plant's second-order transfer function H(f), such as the gain K, the damping factor ζ, the natural frequency f, in response to changes in the correlation between the pump speed and the LVSP. N and / or a delay time L. In some embodiments, the system identification module 940 can be configured to model the plant using a transfer function other than the second-order transfer function H(f). In some embodiments, the system identification module 950 can be configured to change the plant transfer function based on the sensor measurement of the LVSP in response to a change in pump speed.

[0070] Based on the determined changes in the plant transfer function, the controller design module 960 can 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 can adjust the proportional gain K associated with the controller. p , integral gain K i and differential gain K d One or more of K p , K i and K d The adjustment value is set so that the measured LVSP can respond to the corresponding adjustment of the pump speed to reach the target reference pressure with minimal overshoot and time delay.

[0071] The various illustrative logic blocks, modules, circuits, and algorithmic operations described in conjunction with the embodiments disclosed herein can be implemented as electronic hardware, computer software, or a combination of the two. In order to clearly illustrate this interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and operations have been described above in general terms according to their functional aspects. Whether this functionality is implemented as hardware or software depends on the specific application and the design constraints imposed on the entire system. The technician can implement the described functions in a variety of ways for each specific application, but this implementation decision should not be interpreted as causing a departure from the scope of the claims.

[0072] The hardware for implementing the various illustrative logics, logic blocks, modules, and circuits described in conjunction with the aspects disclosed herein may be implemented or executed with a general purpose processor, digital signal processor (DSP), application specific integrated circuit ASIC, 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 alternatively, the processor may be any conventional processor, controller, microcontroller, or state machine. The processor may also be implemented as a combination of receiver smart objects, for example, a combination of a DSP and a microprocessor, two or more microprocessors, one or more microprocessors combined with a DSP core, or any other such configuration. Optionally, some operations or methods may be performed by circuits for a given function.

[0073] 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 codes on a non-transitory computer-readable storage medium or a non-transitory processor-readable storage medium. The operation of the method or algorithm disclosed herein may be embodied in a processor-executable software module or a processor-executable instruction, which 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 accessible by a computer or processor. By way of example and not limitation, such a non-transitory computer-readable or processor-readable storage medium may include RAM, ROM, EEPROM, EEPROM, flash memory, CD-ROM or other optical disk storage, disk storage or other magnetic storage smart objects, or any other medium that can be used to store the required program code in the form of an instruction or data structure and can be accessed by a computer. Disks and optical disks (discs) as used herein include compact disks (CDs), laser optical disks, optical disks, digital versatile disks (DVDs), floppy disks, and Blu-ray disks, wherein disks typically copy data magnetically, while optical disks copy data optically by lasers. The above combinations 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 a computer-readable storage medium, which may be incorporated into a computer program product.

[0074] The foregoing 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 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. Therefore, the present disclosure is not intended to be limited to the embodiments shown herein, but to be consistent with the widest scope consistent with the following claims and the principles and novel features disclosed herein.

Claims

1. A system for controlling a heart pump, comprising: A heart pump comprising: a first portion configured to be positioned within a patient's heart; a first sensor positioned within a first portion of the heart pump and configured to generate an output for measuring or calculating left ventricular systolic pressure within a left ventricle of the patient; and a controller coupled to the heart pump and configured to measure or calculate the left ventricular systolic pressure 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 left ventricular systolic pressure, wherein the heart pump has a pumping speed and a flow rate, and the controller is configured to control one or more of the pumping speed and the flow rate of the heart pump such that the left ventricular systolic pressure within the left ventricle is maintained at a target reference pressure, and Wherein the controller is configured to set the target reference pressure to a fraction of an end-systolic pressure in a normal ejection pulse, wherein the end-systolic pressure is measured by the first sensor, and wherein the fraction is between 0.2 and 0.

4.

2. A system for controlling a heart pump, comprising: A heart pump comprising: a first portion configured to be positioned within a patient's heart; a first sensor positioned within a first portion of the heart pump and configured to generate an output for measuring or calculating left ventricular systolic pressure within a left ventricle of the patient; and a controller coupled to the heart pump and configured to measure or calculate the left ventricular systolic pressure 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 left ventricular systolic pressure, wherein the heart pump has a pumping speed and a flow rate, and the controller is configured to control one or more of the pumping speed and the flow rate of the heart pump such that the left ventricular systolic pressure within the left ventricle is maintained at a target reference pressure, and The system further includes a second sensor positioned within a second portion of the heart pump and configured to generate an output for measuring or calculating mean aortic pressure, and wherein the controller is configured to set the target reference pressure to a fraction of the mean aortic pressure, wherein the fraction is between 0.2 and 0.

4.

3. A system for controlling a heart pump, comprising: A heart pump comprising: a first portion configured to be positioned within a patient's heart; a first sensor positioned within a first portion of the heart pump and configured to generate an output for measuring or calculating left ventricular systolic pressure within a left ventricle of the patient; and a controller coupled to the heart pump and configured to measure or calculate the left ventricular systolic pressure 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 left ventricular systolic pressure, wherein the heart pump has a pumping speed and a flow rate, and the controller is configured to control one or more of the pumping speed and the flow rate of the heart pump such that the left ventricular systolic pressure within the left ventricle is maintained at a target reference pressure, and The controller is configured to set the target reference pressure to reduce a pressure-volume area of ​​the left ventricle, wherein the controller estimates the pressure-volume area based on one or more measurements of measured or calculated left ventricular systolic pressure and left ventricular volume.

4. The system of claim 3, wherein the controller is configured to set the target reference pressure to reduce the pressure-volume area of ​​the left ventricle by 90% to 97%.

5. The system of claim 3, wherein the controller is configured to set the target reference pressure to reduce myocardial oxygen consumption of the left ventricle, wherein the controller estimates the myocardial oxygen consumption based on a linear relationship between the myocardial oxygen consumption and the pressure-volume area.

6. The system of claim 5, wherein the controller is configured to set the target reference pressure to reduce the myocardial oxygen consumption of the left ventricle by 45% to 48.5%.

Images