Systems and methods for system identification

Abstract

To determine appropriate levels of mechanical circulatory support to be provided to a patient.SOLUTION: Systems and methods described herein determine metrics of cardiac or vascular performance, such as cardiac output, and can use these metrics to determine appropriate levels of mechanical circulatory support to be provided to a patient. The systems and methods determine cardiac performance such as cardiac output by: determining aortic pressure measurements 300 within a single heartbeat or across multiple heartbeats; and using such measurements in conjunction with flow estimations or flow measurements made during the single heartbeat or multiple heartbeats to determine the cardiac performance. By utilizing a mechanical circulatory support system placed within the vasculature, the need to place a separate measurement device within a patient is reduced or eliminated. The systems and methods may characterize cardiac performance without altering the operation of a heart pump.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit of U.S. Provisional Patent Application No. 62 / 687,133, entitled "METHODS AND SYSTEMS FOR IMPROVED ASSESSMENT OF VASCULAR AND CARDIAC STATE," filed June 19, 2018, U.S. Provisional Patent Application No. 62 / 863,136, entitled "SYSTEMS AND METHODS FOR SYSTEM IDENTIFICATION," filed June 18, 2019, and U.S. Provisional Patent Application No. 62 / 863,146, entitled "SYSTEMS AND METHODS FOR DETERMINING CARDIAC PERFORMANCE," filed June 18, 2019, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] background Cardiovascular disease is a leading cause of illness, death, and healthcare burden worldwide. Various modalities of treatment have been developed for cardiac health, ranging from pharmaceuticals to mechanical devices and transplants. Temporary cardiac assist devices, such as cardiac pump systems, provide hemodynamic support and promote cardiac recovery. Some cardiac pump systems, such as the IMPELLA® family of devices (Abiomed, Inc., Danvers, Massachusetts), can be inserted percutaneously into the heart and operate in parallel with the native heart to supplement cardiac output. Such cardiac pump systems can measure and / or calculate cardiac pump parameters that are useful in determining the health of the patient and the operation of the cardiac pump system. The pump can be positioned across the aortic valve of the heart, such that the blood inlet to the pump is located in the left ventricle and the outlet from the pump is located in the aorta. In some implementations, the pump is positioned in the right ventricle of the heart. When the pump is placed across the aortic valve, so that the blood inlet to the pump is located in the left ventricle and the outlet from the pump is located in the aorta, the pump contributes to the natural heart action by reducing the load on the left ventricle.

[0003] The duration of cardiac assistance, or the amount of assistance required by each patient, as measured by the volumetric flow rate of blood pumped by the pumping device, can vary. It is difficult for clinicians to directly and quantitatively determine the amount of assistance that should be provided by the device and when to end the use of the cardiac pump system, especially for patients recovering from interventions or other cardiac treatments. Clinicians therefore tend to rely on assessments and indirect estimates of cardiac function, such as using fluid-filled catheters to measure intracardiac or intravascular pressures. In particular, quantification of cardiac output (CO) is difficult. Pulmonary artery catheters (PACs) can provide real-time measurements of central venous and pulmonary artery pressures, and CO can be estimated using Fick's law or bolus thermodilution by measuring systemic oxygen consumption. Due to the assumptions that must be made to arrive at CO metrics, and the lack of fidelity that corresponding more invasive metrics have, PACs have not been able to establish a reliable association with clinical outcomes. PAC measurements do not take into account dynamic changes in cardiac function and are not continuous, but on the other hand do not adequately capture the nonlinear aspects of systemic ventricular-vascular coupling. Summary of the Invention

[0004] overview The systems and methods described herein can determine cardiac performance indicators, such as CO, for a single heartbeat of a patient and use these indicators to determine the appropriate level of mechanical circulatory support to provide to the patient. The cardiac performance indicators can be measured over multiple beats and mathematically processed to arrive at a model of the overall performance of the patient's heart. The determination can be made using a mechanical circulatory support system, such as an intravascular blood pump system. The systems and methods characterize cardiac performance from pressure and flow measurements or pressure and flow estimates during use of the mechanical circulatory support system, determined within the period of a single heartbeat of one or more heartbeats. The systems and methods described herein can be easily validated and utilized in clinical applications because they utilize existing measurements obtained by the mechanical circulatory support system. The systems and methods described herein leverage the operation of an indwelling mechanical circulatory support device to determine CO without the need for additional measurements or catheters. The ability to continuously and accurately track changes in systemic vascular resistance and compliance and estimate cardiac stroke volume represents a significant advance over traditional measurements obtained from PAC or other diagnostics that are easily deployed in clinical practice.

[0005] The described systems and methods determine cardiac performance by determining an aortic pressure measurement (or other physiological measurement) at a single heartbeat or across multiple heartbeats, and using such measurements in combination with flow estimates or measurements made at a single heartbeat or multiple heartbeats to determine cardiac performance, such as cardiac output. Utilizing a mechanical circulatory assist system placed in the vasculature reduces or eliminates the need to place a separate measurement device in the patient. Because measurements can be made at a single heartbeat, cardiac performance at one or more beats can be characterized in a continuous manner from one beat to another, e.g., cardiac performance can be measured for each heartbeat in a series of heartbeats. Furthermore, the operation of the cardiac pump is not impaired by the acquisition of these measurements. The systems and methods described herein can characterize cardiac performance without changing the operation of the cardiac pump (e.g., without increasing or decreasing the pump speed). This can be particularly beneficial when the heart pump speed cannot be reduced without potentially harming the patient because the patient is entirely dependent on the heart pump's blood flow contribution, or when the heart pump speed cannot be increased due to other equipment (e.g., extracorporeal membrane oxygenation (ECMO) systems). In some applications, the systems and methods described herein are used in combination with such other equipment. Thus, the systems and methods described herein can provide a continuous measurement of cardiac performance while providing adequate cardiac assistance.

[0006] Hemodynamic support can be provided to the patient's heart by a mechanical circulatory support system that can include a blood pump, and hemodynamic parameters can be measured during operation of the blood pump. The blood pump can be an intravascular blood pump, an intra-aortic balloon pump, an ECMO device, or other blood pump (e.g., the Impella® family of devices from Abiomed Inc., Danvers, Massachusetts, or the TandemHeart® family of devices from CardiacAssist Inc., Pittsburgh, Pennsylvania). Multiple measurements of hemodynamic parameters can be taken in a single heartbeat. For example, multiple measurements (e.g., 3, 4, 5, 6, 7, 10, 20, 30, 100, or any suitable number of measurements) can be taken in the diastolic downstroke of the heartbeat at various times. When cardiac performance is modeled as a mathematical system (e.g., by the Windkessel model), the pressures and blood flow at these various times can form simultaneous equations that can be solved to determine functional values ​​such as systemic vascular resistance and compliance that represent cardiac performance. Cardiac output (as well as other indicators that represent cardiac and / or vascular performance) can then be calculated from the resistance or compliance values. These calculations are not limited to calculating resistance and compliance only once for a single heartbeat; for example, the calculations described herein can include calculating resistance and compliance for multiple pressure measurements (or groups of pressure measurements) at a single heartbeat, determining resistance and compliance from these measurements, and then averaging or otherwise processing these resistance and compliance values ​​to determine representative resistance, compliance, or other indicator values ​​that represent vascular or cardiac health as a whole for a single heartbeat. Similar measurements can be made for multiple heartbeats and used to determine averages or other combined measurements that model the cardiac performance of the patient's heart.

[0007] In some aspects, hemodynamic support can be applied or adjusted based on the determined cardiac performance measurements. Hemodynamic support is applied to the patient's heart by a mechanical circulatory assist device (MCS). In some implementations, the device is an intravascular blood pump that is placed in the patient's heart by percutaneous insertion. The MCS can be a surgically implanted device, a left ventricular assist device, a counterpulsation device, an expandable heart pump, an extracorporeal membrane oxygenation device, an intra-aortic balloon pump, or any other suitable device. The pump can be introduced into the patient because the patient is in cardiogenic shock, undergoing a coronary intervention, having a heart attack, or otherwise facing a decline in cardiac health. The pump contributes to the operation of the native heart such that CO from the heart is equal to native CO plus pump power.

[0008] Providing hemodynamic support can include operating the intravascular blood pump at a first pumping speed or pump rate. The pumping speed is the speed of operation of the pump and corresponds to the amount of blood flow provided by the operation of the pump. In some implementations, the pumping speed can correspond to the rotational speed of the rotor. For example, the pump speed can be 10,000 RPM, 20,000 RPM, 30,000 RPM, 40,000 RPM, 50,000 RPM, 60,000 RPM, 70,000 RPM, 80,000 RPM, 90,000 RPM, 100,000 RPM, or any suitable speed. The pump speed can correspond to a power level or P level, as described below in connection with FIG. 1. For example, the pump speed can be P-1, P-2, P-3, P-4, P-5, P-6, P-7, P-8, or P-9. In some implementations, the pumping speed may instead correspond to the rate at which the pump's chamber fills with blood and expels blood.

[0009] In some implementations, the hemodynamic support is provided at a first pumping rate for multiple beats of the heart. Each beat includes a systolic upstroke, a dicrotic notch, and a diastolic downstroke that occurs after the dicrotic notch. For example, the hemodynamic pumping rate can be provided for 2, 3, 4, 10, 20, 30, 100, 200, or any other suitable number of heartbeats. The dicrotic notch marks the beginning of diastole, which is the phase of the heartbeat during which the myocardium relaxes to allow the ventricles to fill with blood. In the case of an intravascular blood pump being a left-sided heart, when the blood pump is operating, the only substantial flow from the patient's left ventricle to the aorta during diastole is the flow contributed by the blood pump. Diastole is the time until the heart completes diastole, and is the phase of the heartbeat during which the myocardium relaxes to allow the ventricles to fill with blood. For example, the diastole may be 0.05 seconds, 0.1 seconds, 0.2 seconds, 0.3 seconds, 0.4 seconds, 0.5 seconds, 0.6 seconds, 0.7 seconds, 0.8 seconds, 0.9 seconds, 1 second, or any suitable length.

[0010] In some implementations, hemodynamic parameters are measured to monitor the location and function of the device and the health of the patient while on the device. For example, hemodynamic parameters can be measured with a sensor included in the intravascular blood pump or can be measured by a separate device. Hemodynamic parameters can be any parameter related to the flow of blood in an organ or tissue of the body. For example, hemodynamic parameters can be heart rate, blood pressure, arterial oxygen saturation, mixed venous saturation, central venous oxygen saturation, arterial blood pressure, mean arterial pressure, right arterial pressure, central venous pressure, right ventricular pressure, pulmonary artery pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, left atrial pressure, aortic pressure, pressure difference, left ventricular end pressure, stroke volume, stroke volume index, stroke volume variation, systemic vascular resistance, systemic vascular resistance index, pulmonary vascular resistance, pulmonary vascular resistance index, pulmonary vascular resistance, pulmonary vascular resistance index, left ventricular stroke work ... These may include at least one or more of: ventricular stroke work index, right ventricular stroke work, right ventricular stroke work index, coronary artery perfusion pressure, right ventricular end diastolic volume, right ventricular end diastolic volume index, right ventricular end systolic volume, right ventricular ejection fraction, arterial oxygen content, venous oxygen content, arterial-venous oxygen content difference, oxygen delivery, oxygen delivery index, oxygen consumption, oxygen consumption index, oxygen uptake rate, oxygen uptake index, total peripheral resistance, CO, cardiac index, and CPO.

[0011] In some implementations, the hemodynamic parameter is aortic pressure. Multiple aortic pressure measurements can be taken at different times, and the results are used to detect the pump's position and function and set the pump for operation. In some implementations, three or more aortic pressure measurements are detected, which may all be within the diastole of the same heartbeat of multiple beats, or may be during different beats or times. If the blood pump is a left-sided heart, pressure measurements during diastole may be optimal, since the substantial flow through the aorta during diastole is only due to the contribution of the blood pump. Thus, the pump's function and contribution to the heart may be easier to determine.

[0012] In some implementations, at least three blood flow rates pumped by the intravascular blood pump are determined at three different times. p ) can be determined by the pump's speed (revolutions per minute or RPM) and the motor current supplied to the pump to maintain that pump speed. The technical relationship between pump speed and motor current allows the flow rate to be estimated by a mathematical correlation or a look-up table (where pump speed and motor current are linked to the look-up table). The flow rate values ​​in the look-up table may be pre-populated by bench testing. Another way to determine the flow rate output from a pump is to determine the flow rates for some of the possible combinations of pump speed and motor current values ​​before placing the pump (or a similar pump) on a patient. For example, if the flow rate at a pump speed of 40,000 RPM and motor current of 500 mA is represented by i1 and the flow rate at a pump speed of 40,000 RPM and motor current of 510 mA is represented by i2, the flow rate at a pump speed of 40,000 RPM and motor current of 505 mA can be calculated by taking the average of i1 and i2.

[0013] CO is determined based on multiple aortic pressure measurements and blood flow velocities. Some applications use at least three aortic pressure measurements and at least three corresponding blood flow velocities. In one example, two current sources i in parallel with each other are used to simulate a vascular system. h and i p The Windkessel model is used, with resistance R and compliance C. The governing equations of the technical relationships reflected in this model are:

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[0014] The systemic vascular resistance and compliance values ​​can be used to calculate other indices of cardiac performance. For example, once R and C are determined using the Windkessel model described above, the calculated values ​​of R and C can be inserted into equation (1) above to obtain i h To determine the volumetric flow contributed by the intrinsic cardiac function, CO can be calculated by calculating the total cardiac blood flow (i h +i p ) can be calculated by taking the average

[0015] In some implementations, another index representing cardiac performance can be determined. For example, the index representing cardiac performance can be ventricular resistance, ventricular compliance, CO, CPO, stroke volume, stroke work, ejection fraction, cardiac index, or patient survival prediction. Many indexes representing cardiac performance are interrelated. For example, CO is determined based on the flow rate of blood through the pump. Stroke volume is an index of left ventricular function, and its formula is SV=CO / HR, where SV is stroke volume, CO is cardiac output, and HR is heart rate. Stroke work is the work done by the ventricle to eject blood, and can be calculated from the stroke volume according to the formula SW=SV*MAP, where SW is stroke work, SV is stroke volume, and MAP is mean arterial pressure. Cardiac work is calculated by the product of stroke work and heart rate. CPO is a measure of cardiac function that represents the pumping power of the heart, and is expressed in watts. CPO is calculated using the formula CPO=mAoP*CO / 451, where CPO is cardiac power output, mAoP is mean arterial pressure, CO is cardiac output, and 451 is a constant used to convert mmHg x L / min to watts. Ejection fraction can be calculated by dividing stroke volume by ventricular blood volume. Other parameters such as chamber pressure, preload state, afterload state, cardiac recovery, flow loading state, variable volume loading state, and / or cardiac cycle flow state can be calculated from or determined via these parameters.

[0016] The operation of the pump can be adjusted based on the indicators representing cardiac performance. Adjustments to the pump operation can include increasing the pump speed, decreasing the pump speed, adjusting the pump placement, turning the pump off, or any other suitable adjustment. For example, if the total amount of blood being pumped is below a threshold, the pump speed can be increased, while if the amount of blood is above a threshold, the pump speed can be decreased.

[0017] In some implementations, a plurality of aortic pressure measurements are detected at the diastolic downstroke of a particular one of the plurality of beats. For example, pressure can be sampled at a rate of 1, 2, 3, 10, 20, 30, 100, 200, 300, 1000, 2000, 3000, or any other suitable number of samples per second. In some examples, the aortic pressure is sampled only at the diastolic downstroke. In some examples, the aortic pressure is measured constantly or periodically. In some examples, the sampling rate of the aortic pressure is changed during the diastolic downstroke. In some implementations, at least one aortic pressure measurement is taken at the end of diastole when cardiac output is generated solely by the action of the blood pump. In some implementations, the plurality of aortic pressure measurements can be obtained by a pressure sensor. For example, the pressure sensor can be part of an intravascular blood pump that provides hemodynamic assistance to the heart, or the pressure sensor can be separate from the intravascular blood pump.

[0018] In some implementations, determining the cardiac output of the patient's heart includes processing multiple cardiac output values ​​for a single heartbeat or multiple heartbeats. For example, as described above, multiple aortic pressure measurements can be taken at the diastole of a particular heartbeat. For each pressure measurement of the multiple aortic pressure measurements, pressure can be measured and flow can be estimated. The pressure and flow values, in combination with the known measurement time points, can be compared between two time points to calculate cardiac parameters such as vascular resistance and compliance, which can then be used to determine CO. Even within a single heartbeat, the calculated CO value throughout the diastolic decline can vary due to patient cardiac variability and differences in flow estimation. Processing the multiple CO values ​​can include performing at least one of summing, averaging, or linear regression on the determined multiple cardiac output values ​​to calculate a first cumulative indicator of cardiac output. By processing multiple CO values ​​for multiple aortic pressure measurements in a single heart, the systems and methods described herein provide an accurate representation of cardiac CO (and cardiac performance). In some implementations, the first cumulative indicator of the cardiac output of the heart represents cardiac performance at a particular heart beat or overall patient health.

[0019] In some implementations, the systems and methods herein can determine cardiac performance by calculating CO for multiple heartbeats, and the CO measurements and determinations can be evaluated to identify a cumulative indicator of cardiac performance of the heart. In some implementations, a second cumulative indicator of cardiac output of the heart is determined for a second heartbeat after the particular heartbeat described above, i.e., the first cumulative indicator of cardiac output can represent the first heartbeat at a first time point, and the second cumulative cardiac output can represent the second heartbeat at a second time point that is later than the first time point. In some implementations, the second heartbeat immediately follows the first heartbeat. In some implementations, a period of time elapses between the end of the first heartbeat and the beginning of the second heartbeat. This period of time can be 1 second, 1 minute, 10 minutes, 1 hour, 10 hours, or any other suitable length of time. For example, a first cumulative indicator can be calculated for heartbeats beginning at 12:00 p.m., and a second cumulative indicator can be calculated for heartbeats beginning at 1:00 p.m. on the same day. Examining the cardiac output of the heart at various points in time can enable a clinician or computer system to spot overall trends in the patient's health.

[0020] In some implementations, the first cumulative indicator of cardiac output is compared to a second cumulative indicator of cardiac output. Similar to the first cumulative indicator described above, the second cumulative indicator can be determined by calculating a second plurality of cardiac output values, each cardiac output value of the second plurality of cardiac output values ​​corresponding to a beat of the second set of beats. A sum, average, or linear regression is applied to the determined plurality of cardiac output values ​​to calculate a second cumulative indicator that can represent the overall cardiac performance of the patient's heart.

[0021] Based on a comparison between the first cumulative indicator and the second cumulative indicator, either (i) improved cardiac performance of the heart or (ii) a decline in cardiac performance of the heart is determined. The improved or declined cardiac performance may be indicative of the patient's cardiac or overall health. Similarly, CO values ​​may be determined for multiple heartbeats of the patient and may be used to track cardiac performance over time. Hemodynamic support provided to the patient may be adjusted based on a determination that the cardiac performance of the heart is improving or declining over time. The indicators may be used to identify the timing and extent of application and level adjustment of mechanical circulatory support. In some implementations, if improved cardiac performance is observed, the hemodynamic support provided to the patient may be reduced, while if a decline in cardiac performance is observed, the hemodynamic support provided to the patient may be increased.

[0022] In some aspects, hemodynamic parameters are monitored while operating the heart pump at the first pump speed. In some implementations, the pump is an intravascular blood pump device that is placed in the patient's heart by percutaneous insertion. The pump may be introduced into the patient because the patient is in a state of cardiogenic shock or otherwise facing declining health. The pump may be placed across the aortic valve such that the blood inlet to the pump (e.g., blood inlet 172 in FIG. 1 ) is located in the left ventricle and the outlet from the pump (e.g., outlet opening 170 in FIG. 1 ) is located in the aorta. The pump contributes to the operation of the native heart such that CO from the heart is equal to native CO plus pump power.

[0023] A hemodynamic parameter may be any parameter related to the flow of blood in an organ or tissue of the body. For example, hemodynamic parameters may be heart rate, blood pressure, arterial oxygen saturation, mixed venous saturation, central venous oxygen saturation, arterial blood pressure, mean arterial pressure, right arterial pressure, central venous pressure, right ventricular pressure, pulmonary artery pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, left atrial pressure, aortic pressure, pressure differential, left ventricular end pressure, stroke volume, stroke volume index, stroke volume variation, systemic vascular resistance, systemic vascular resistance index, pulmonary vascular resistance, pulmonary vascular resistance index, pulmonary vascular resistance, pulmonary vascular resistance index, left ventricular stroke work, left ventricular The parameters may include at least one of stroke work index, right ventricular stroke work, right ventricular stroke work index, coronary artery perfusion pressure, right ventricular end diastolic volume, right ventricular end diastolic volume index, right ventricular end systolic volume, right ventricular ejection fraction, arterial oxygen content, venous oxygen content, arterial-venous oxygen content difference, oxygen delivery, oxygen delivery index, oxygen consumption, oxygen consumption index, oxygen uptake budget, oxygen uptake index, total peripheral resistance, CO, cardiac index, and cardiac output (CPO). The pump speed is the speed of operation of the pump and corresponds to the amount of blood flow provided by the operation of the pump. In some implementations, the pump speed may correspond to the rotational speed of the rotor. For example, the pump speed may be 10,000 RPM, 20,000 RPM, 30,000 RPM, 40,000 RPM, 50,000 RPM, 60,000 RPM, 70,000 RPM, 80,000 RPM, 90,000 RPM, 100,000 RPM, or any suitable speed. The pump speed may correspond to a power level or P level, as described above in connection with FIG. 1. For example, the pump speed may be P-1, P-2, P-3, P-4, P-5, P-6, P-7, P-8, P-9, or any other suitable value. In some implementations, the pump speed may instead correspond to the rate at which the pump's chambers fill with and expel blood. By monitoring a hemodynamic parameter, the systems and methods described herein can investigate changes in that hemodynamic parameter over time. Such a comparison can be used to quantify cardiac performance.

[0024] In some implementations, the diastole of a cardiac cycle is identified based on the shape of the hemodynamic parameters over time. In particular, the dicrotic notch (e.g., evident in the aortic pressure waveform, such as notch 310 in FIG. 3) indicates the beginning of diastole. If the patient's heart rate is relatively stable, the beginning of a cardiac cycle can be accurately predicted. As the cardiac cycle completes systole, the aortic pressure drops before rising to form the dicrotic notch. Identifying the shape of this waveform allows the system to determine the beginning of diastole. Diastole is the time it takes for the heart to complete diastole, the phase of the cardiac cycle in which the myocardium relaxes and allows the ventricles to fill with blood. For example, diastole can be 0.05 seconds, 0.1 seconds, 0.2 seconds, 0.3 seconds, 0.4 seconds, 0.5 seconds, 0.6 seconds, 0.7 seconds, 0.8 seconds, 0.9 seconds, 1 second, or any suitable length.

[0025] In some implementations, a time-variant relationship between aortic pressure and blood flow during diastole is determined. The time-variant relationship is determined by two current sources i h and i p The model may be a Windkessel model with a resistance R and a compliance C. The governing equation of this model is:

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[0026] In some implementations, the total amount of blood pumped per heartbeat, which represents cardiac performance, is calculated based on the time-varying relationship between aortic pressure and blood flow during diastole. For example, once R and C are determined, the calculated values ​​of R and C are substituted into equation (1) above to obtain i h Cardiac CO can be determined by solving for:

[0027] In some implementations, another index representing cardiac performance can be calculated. For example, the index representing cardiac performance can be ventricular resistance, ventricular compliance, CO, CPO, stroke volume, stroke work, ejection fraction, cardiac index, or patient survival prediction. Many indexes representing cardiac performance are interrelated. For example, CO is determined based on the flow rate of blood through the pump. Stroke volume is an index of left ventricular function, and its formula is SV=CO / HR, where SV is stroke volume, CO is cardiac output, and HR is heart rate. Stroke work is the work done by the ventricle to eject blood, and can be calculated from the stroke volume according to the formula SW=SV*MAP, where SW is stroke work, SV is stroke volume, and MAP is mean arterial pressure. Cardiac work is calculated by the product of stroke work and heart rate. CPO is a measure of cardiac function that represents the pumping power of the heart, and is expressed in watts. CPO is calculated using the formula CPO=mAoP*CO / 451, where CPO is cardiac power output, mAoP is mean arterial pressure, CO is cardiac output, and 451 is a constant used to convert mmHg x L / min to watts. Ejection fraction can be calculated by dividing stroke volume by ventricular blood volume. Other parameters such as chamber pressure, preload state, afterload state, cardiac recovery, flow loading state, variable volume loading state, and / or cardiac cycle flow state can be calculated from or determined via these parameters.

[0028] In some implementations, pump operation is adjusted based on the indicators representative of cardiac performance. Adjustments to pump operation may include increasing pump speed, decreasing pump speed, adjusting pump placement, turning off the pump, or any other suitable adjustment. For example, pump speed may be increased when the total amount of blood being pumped is below a threshold, while pump speed may be decreased when the amount of blood is above a threshold.

[0029] In some implementations, the method includes operating a blood pump within the patient's vasculature and determining a cardiac output of the patient's heart using any of the systems and sensors described above. A pumping speed of the blood pump can be adjusted based on the determined cardiac output. In some implementations, the applied hemodynamic support can be based on a determination that the cardiac performance of the heart is improving or deteriorating over time.

[0030] In some implementations, a vascular sensor is provided. The vascular sensor can include a system for generating blood flow in a patient's blood vessel. The system can be an intravascular system. The system can include a motor and an impeller. In some implementations, the system for generating blood flow in a patient's blood vessel includes a cannula configured to extend into a left ventricle of the heart and a pressure sensor configured to detect at least one of an aortic pressure, a left ventricular pressure, or a differential pressure. The system for generating blood flow in a patient's blood vessel can be an intracardiac blood pump incorporating an impeller within a shroud. For example, the shroud can be a pump housing. The shroud can be sized to pass through the patient's blood vessel and can be coupled to a motor or other pump element. The shroud can include one or more blood outlets or outlets.

[0031] Additionally, the vascular sensor can include a controller. The controller can be configured to detect changes in the resistance of the impeller rotation within the blood vessel. In some implementations, a constant impeller rotation speed is maintained based on the detected resistance of the impeller rotation.

[0032] In some implementations, the vascular compliance and vascular resistance can be calculated based on the change in resistance of the impeller rotation using a transfer function. In some implementations, the transfer function is a Windkessel model. In some implementations, the pump operation data can be transmitted to a computing device. The computing device can be located separately from the controller or can be on-board the controller. For example, the computing device can be a remotely stored server. In some implementations, the pump operation data includes at least one of a pressure measurement, a current measurement, a change in resistance of the impeller rotation, and an estimate of a flow rate. In some implementations, the controller is further configured to receive pump operation commands from the computing device, the pump operation commands being based on the pump operation data. For example, the computing device can calculate the vascular resistance and compliance and modify the pump operation accordingly.

[0033] In some implementations, the controller or computing device is configured to determine an index representative of cardiac performance based on the vascular compliance and vascular resistance. The index representative of cardiac performance may be at least one of cardiac output, cardiac power, stroke volume, stroke work, ejection fraction, cardiac contractility, ventricular elastance, cardiac index, patient survival prediction, or any suitable index.

[0034] In some implementations, the controller is configured to adjust the impeller rotational speed based on at least one of vascular resistance, vascular compliance, or cardiac output. For example, the impeller rotational speed can be increased or decreased to provide more or less blood flow based on the patient's cardiac or vascular health.

[0035] In some implementations, the controller is configured to receive measurements representative of aortic pressure over a period of time, detect a current supplied to the pump, and determine a rate of blood flow pumped by the system over that period based on the current supplied to the pump. Calculations of vascular compliance and vascular resistance can be based on the measurements representative of aortic pressure and the rate of blood flow.

[0036] In some implementations, the controller is configured to perform any of the implementations, aspects, and methods described herein. For example, the controller may be an Automated Impella Controller (AIC) from Abiomed, Inc., or any other suitable controller. In some implementations, the heart pump system includes a catheter, a motor, a rotor operably coupled to the motor, a pump housing at least partially surrounding the rotor, one or more sensors, such as a differential pressure sensor, and a controller, and actuating the motor drives the rotor and pumps blood through the pump housing. For example, the heart pump system may include an Impella 5.0 heart pump from Abiomed, Inc., connected to an AIC or any other suitable system.

[0037] In some implementations, the controller includes a display. Any of the above-mentioned calculations or functions can be configured for display. For example, an aortic pressure waveform can be presented on a graphical user interface. A clinician can view such a display and adjust the operation of the pump based on observations of the hemodynamic parameters over time. [Brief description of the drawings]

[0038] [Figure 1] 1 illustrates an exemplary heart pump system inserted into a patient's blood vessel. [Diagram 2]1 illustrates a process for determining the amount of blood pumped per heart beat according to a particular implementation. [Diagram 3] 1 illustrates a plot of pressure versus time for a heart pump system in accordance with certain implementations. [Figure 4] 1 illustrates a CO sensor coupled to a patient according to certain implementations. [Diagram 5] 1 illustrates a process for determining the total amount of blood pumped per heart beat according to a particular implementation. [Figure 6] 1 illustrates a process for determining cardiac output according to certain implementations. [Figure 7] 1 illustrates pressure versus time and flow versus time plots of a heart pump system in accordance with certain implementations. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0039] Detailed Description Certain exemplary aspects will be described to provide an overall understanding of the systems and methods described herein. Although the aspects and features described herein are specifically described for use in connection with a percutaneous heart pump system, it will be appreciated that all of the components and other features outlined below can be combined with one another in any suitable manner and are adaptable and applicable to other types of cardiac therapy and heart pump systems, such as heart pump systems implanted using surgical incisions.

[0040] The systems, devices, and methods described herein allow for the evaluation of the function of an organ by an assist device located completely or partially within the organ. In particular, the systems, devices, and methods allow for the evaluation of the function of the heart using a mechanical circulatory assist system, such as a percutaneous ventricular assist device. For example, an assist device, such as a blood pump, can be used to treat cardiogenic shock or heart attack, or generally to assist the heart during a coronary intervention.

[0041] Evaluating cardiac function using a mechanical circulatory support system can alert medical professionals to changes in cardiac function and allow the degree / level of assistance provided by the assist device (i.e., the flow rate of blood pumped by the device) to be tailored to the needs of a particular patient. For example, the degree of assistance can be increased when the patient's cardiac function is deteriorating, or decreased when the patient's cardiac function recovers and returns to a baseline of normal cardiac function. This can allow the device to dynamically respond to changes in cardiac function to promote cardiac recovery and can allow the patient to be gradually weaned off therapy. Additionally, evaluation of cardiac function can indicate when it is appropriate to terminate use of the cardiac pump system. Although some embodiments presented herein are directed to a cardiac pump system implanted across the aortic valve and partially located in the left ventricle, the concepts are applicable to devices within other areas of the heart, cardiovascular system, or body.

[0042] The assessment of cardiac function can include determining cardiac parameters utilizing the heart and device interaction. The systems and methods described herein determine cardiac output based on aortic pressure measurements and flow output from a blood pump system. The flow can be a measurement or an estimate determined from the motor current supplied to the motor at a given pump speed of the intravascular blood pump system. At least one advantage of the systems and methods described herein is that the cardiac pump system allows assessment of cardiac function without modifying the pump operation (e.g., pump speed), thereby minimizing risks associated with changing pump speed. Increased pump speed can lead to aspiration or other risks, while decreased pump speed is accompanied by reduced patient assistance. Furthermore, frequent and / or abrupt changes in pump speed can lead to hemolysis or reduced pump / motor performance. Furthermore, using an intravascular blood pump system to measure or estimate parameters necessary to determine indices representative of cardiac performance allows for continuous measurement of cardiac performance, since these indices are obtained by a blood pump system already placed in the patient's vasculature.

[0043] Continually measuring vascular and cardiac performance by leveraging the action of the heart pump system is an important step to provide additional clinical data that aids in titrating appropriate device support. More importantly, however, the systems and methods described herein demonstrate the impact and potential of device-arterial coupling in determining cardiac and vascular status. Unlike some invasive heart pump systems that shunt blood away from the heart, the heart pump system presented herein resides within the heart and functions in parallel with native ventricular function. This allows the heart pump system presented herein to have sufficient sensitivity to detect native ventricular function, unlike some more invasive devices. Thus, the systems, devices, and methods allow the heart pump system to be used not only as an auxiliary device, but also as a diagnostic and prognostic tool. The heart pump system can essentially function as an active catheter that extracts information about cardiac function by hydraulically coupling to the heart. In some implementations, the heart pump system operates at a constant level (e.g., a constant rotational speed of the rotor) while the power delivered to the auxiliary device is measured. In certain implementations, the speed of the rotor of the heart pump system can be varied (eg, as a delta, step, or ramp function) to further explore native heart function.

[0044] FIG. 1 illustrates an exemplary heart pump system inserted into a patient's blood vessel. A heart pump system compatible with the present disclosure is disclosed in U.S. Patent Application Publication No. 2018-0078159-A1, the contents of which are incorporated herein by reference in their entirety. In general, any other heart pump system or system for acquiring physiological data from a patient can be used with the present disclosure. In some implementations, the systems and methods described herein may relate to the IMPELLA® family of devices (Abiomed, Inc., Danvers, Massachusetts).

[0045] The heart pump system 100 may operate within the heart, partially within the heart, external to the heart, partially external to the heart, partially external to the vasculature, or at any other suitable location in the patient's vasculature. The heart pump system may be considered "in place" when the cannula 173 is positioned across the aortic valve such that the blood inlet to the pump (e.g., blood inlet 172) is located in the left ventricle and the outlet from the pump (e.g., outlet opening 170) is located in the aorta. The heart pump system 100 includes a heart pump 106 and a control system 104. All or part of the control system 104 may be in a controller unit separate / remote from the heart pump 106. In some implementations, the control system 104 is internal to the heart pump 106. The control system 104 and the heart pump 106 are not shown to scale. The pump system 100 includes an elongated catheter body 105, a motor housing 102, and a drive shaft from which the pump elements are formed. Pump 100 includes a pump housing 134 and a motor housing 102 that rotates impeller blades on a drive shaft, which is coupled to a cannula 173 at a distal end 111 of the motor housing 102, within the pump housing 134 to generate blood flow into the cannula 173 at a suction head 174. The suction head 174 provides a blood inlet 172 at a distal end portion 171 of the cannula 173. A flow of blood 109 passes through the cannula 173 in a first direction 108 and exits the cannula 173 at one or more exit openings 170 of the cannula 173.

[0046] Additionally, rotation of the drive shaft within the pump housing 134 can rotate the pump elements within the bearing gap. A hemocompatible fluid can be delivered through the elongated catheter 105 and through the motor housing 102 to the proximal end portion of the cannula 173, where the fluid is pressurized by the rotation of the pump elements. The flow of the hemocompatible fluid has a second direction 122 through the bearing gap of the pump. After exiting the bearing gap, the hemocompatible fluid can mix with the flow of blood and flow with the blood to the aorta according to flow direction 123.

[0047] The heart pump 100 is inserted into the patient's blood vessel through the sheath 175. The pump housing 134 can enclose the rotor and internal bearings and can be sized to be inserted percutaneously into the patient's blood vessel. In some implementations, the pump can be advanced through the vascular system and past the aortic arch 164. Although the pump is illustrated in the left ventricle, the pump can instead be positioned in the right heart to pump blood from the patient's inferior vena cava or right atrium through the right ventricle and into the pulmonary artery.

[0048] To optimally position the heart pump 100 in a blood vessel or ventricle, the distal end portion 171 of the cannula 173 may further include a flexible protrusion 176 distal to the suction head 174. The flexible protrusion 176 may prevent the suction head 174 from approaching the wall of the blood vessel and possibly sticking to the wall of the vessel due to suction. Since the flexible protrusion 176 may not have suction, the flexible protrusion 176 may extend the pump 100 mechanically but not fluidically. In some implementations, the flexible protrusion may be formed as a pigtail. In some aspects, the pump may not necessarily include a flexible protrusion.

[0049] The elongate catheter 105 houses a connection 126 which may comprise a fluid supply line and may also house an electrical connection cable. The connection 126 may supply a hemocompatible fluid to the pump from a fluid reservoir which may be housed within the control system 104.

[0050] The control system 104 includes a controller 182 and controls the pump 106, for example, controlling power to the motor or controlling the motor speed. In some implementations, the control system 104 includes a display screen for displaying measurements such as a differential pressure signal and motor current. The control system 104 can include circuitry for monitoring the motor current for a drop in current indicating air in the line, monitoring a change in the differential pressure signal, monitoring flow position, monitoring suction, or any other suitable measurement. The control system 104 can include warning sounds, lights, or indicators to alert the operator to a sensor failure, a disconnected or broken connection 126, or a sudden change in the patient's health.

[0051] The motor 108 can be operated at a speed necessary to maintain the rotor at a set speed. As a result, the motor current that the motor draws to maintain the rotor speed can be monitored and used to understand the underlying condition of the heart, as described further below. For example, the motor current can be used to determine the flow rate through the heart.

[0052] The heart pump can operate at various pump speeds or P levels. P levels are performance levels of the heart pump system and are related to the flow control of the system. Higher P levels increase the flow rate, motor current, and revolutions per minute for the heart pump system, and thus higher P levels correspond to higher flow rates and higher revolutions per minute for the heart pump system. For example, power level P-1 can correspond to a first number of revolutions per minute (RPM) of the rotor, while power level P-2 can correspond to a second number of RPM. In some examples, the pump operates at ten different power levels ranging from P-0 to P-9. These P levels can correspond to 0 RPM to 100,000 RPM or any suitable number. As the rotor speed changes, the CO of the heart changes.

[0053] The control system 104 may include a current sensor (not shown). The controller 182 provides current to the motor 108 by connection 126, such as via one or more wires. The current provided to the motor 108 via connection 126 is measured by the current sensor. The load experienced by the motor of a mechanical pump is the pressure head, or the difference between the aortic pressure and the left ventricular pressure. The heart pump 106 experiences a nominal load in steady state operation at a given pressure head, and any variation from this nominal load is the result of changes in external loading conditions, such as the mechanics of left ventricular contraction. Changes in dynamic loading conditions change the motor current required to operate the pump rotor at a constant or substantially constant speed. As described above, the motor may be operated at a speed required to maintain the rotor at a set speed, and the motor current drawn by the motor to maintain the rotor speed may be monitored to understand the underlying cardiac condition. The cardiac condition may be even more accurately quantified and understood by simultaneously monitoring the pressure head during the cardiac cycle using the pressure sensor 112. A cardiac parameter estimator 185 receives the current signal from the current sensor and the pressure signal from the pressure sensor 112. The cardiac parameter estimator 185 uses these current and pressure signals to characterize the function of the heart. The cardiac parameter estimator 185 can access stored lookup tables to obtain additional information to characterize the function of the heart based on the pressure and current signals. For example, the cardiac parameter estimator 185 can receive the aortic pressure from the pressure sensor 112 and can use the lookup table to determine the delta pressure between the aorta and the ventricle using the motor current and pump speed.

[0054] In some implementations, the pressure sensor 112 is an aortic pressure sensor. In some implementations, the pressure sensor 112 is a flexible membrane integrated into the cannula 172 configured to measure differential pressure. One side of the sensor is exposed to blood pressure outside the cannula, and the other side is exposed to blood pressure inside the cannula. The sensor generates an electrical signal (differential pressure signal) proportional to the difference between the pressure outside and inside the cannula, which may be displayed by the heart pump system. When the heart pump system is correctly positioned across the aortic valve, the top (outer surface) of the sensor is exposed to the aortic pressure, and the bottom (inner surface) of the sensor is exposed to the intraventricular pressure. Thus, the differential pressure signal is approximately equal to the difference between the aortic pressure and the intraventricular pressure. In some implementations, the system includes both a differential pressure sensor and an aortic pressure sensor.

[0055] FIG. 2 illustrates a process 200 for determining cardiac output. The process 200 can be performed using the heart pump system 100 of FIG. 1 or any other suitable pump. In some implementations, the pump is an intravascular blood pump device that is placed in the patient's heart by percutaneous insertion. The pump may be introduced into the patient because the patient is in a state of cardiogenic shock or otherwise facing declining health. The pump may be placed across the aortic valve such that the blood inlet to the pump (e.g., blood inlet 172 of FIG. 1) is located in the left ventricle and the outlet from the pump (e.g., outlet opening 170 of FIG. 1) is located in the aorta. The pump contributes to the operation of the native heart such that CO from the heart is equal to the native CO plus the pump output.

[0056] In step 202, hemodynamic support is applied to the heart at a first pumping speed. In some implementations, the pumping speed may correspond to the rotational speed of the rotor. For example, the pump speed may be 10,000 RPM, 20,000 RPM, 30,000 RPM, 40,000 RPM, 50,000 RPM, 60,000 RPM, 70,000 RPM, 80,000 RPM, 90,000 RPM, 100,000 RPM, or any suitable speed. The pump speed may correspond to a power level or P level, as described below in connection with FIG. 1. For example, the pump speed may be P-1, P-2, P-3, P-4, P-5, P-6, P-7, P-8, or P-9. In some implementations, the pumping speed may instead correspond to the rate at which the pump's chambers fill with and expel blood. The pumping rate is delivered over multiple beats of the heart, each beat including a systolic upstroke, a dicrotic notch, and a diastolic downstroke that occurs after the dicrotic notch.

[0057] At least three aortic pressure measurements are detected at the diastolic downstroke of a particular one of the beats in step 204. In some implementations, the aortic pressure is continuously measured or periodically sampled to detect multiple aortic pressure measurements. For example, the pressure can be sampled at a rate of 1, 2, 3, 10, 20, 30, 100, 200, 300, 1000, 2000, 3000, or any other suitable number of samples per second. In some examples, the aortic pressure is sampled only at the diastolic downstroke. In some examples, the aortic pressure is constantly measured or periodically measured.

[0058] At least three blood flows pumped by the intravascular blood pump are determined in step 206. As shown in FIG. 3 and described above, pressure can be measured at a series of time points during the diastolic period. For each of these pressure measurements, the pressure is measured and the flow rate can be estimated based on the current supplied to the pump to maintain the rotor speed. This mathematical relationship between pump speed and motor current and flow rate estimates can be implemented by setting up a look-up table where the pump speed and motor current are indexes into the table and the flow rate values ​​in the table are pre-populated by bench testing. Another way is to pre-determine the flow rates for some of the possible combinations of pump speed and motor current. For example, if the flow rate at a pump speed of 40,000 RPM and a motor current of 500 mA and the flow rate at a pump speed of 40,000 RPM and a motor current of 510 mA are known as i1 and i2, respectively, the flow rate at a pump speed of 40,000 RPM and a motor current of 505 mA can be calculated by taking the average of i1 and i2. Pressure and flow measurements, in combination with known measurement time points, are compared between the two time points and cardiac parameters such as systemic vascular resistance and compliance are calculated.

[0059] In step 208, cardiac output at a particular beat is determined based on the aortic pressure and blood flow measurements. To simulate aortic pressure, two current sources i h and i p The Windkessel model can be used, with resistance R and compliance C. The governing equations of this model are:

number

number

[0060] Based on the calculated CO value, the operation of the pump can be adjusted. Adjustments to the pump operation can include increasing the pump speed, decreasing the pump speed, adjusting the pump placement, turning the pump off, or any other suitable adjustment. For example, if CO is below a threshold, the pump speed can be increased, while if CO is above a threshold, the pump speed can be decreased.

[0061] FIG. 3 illustrates a plot 300 of pressure versus time for a heart pump system according to a particular implementation. The y-axis of the plot 300 represents aortic pressure (mmHg), while the x-axis represents time as a percentage of the heart beat length. In particular, the plot 300 illustrates that pressure can be measured at a series of time points P0-P5 during the diastole of a heart beat. Δt1 represents the time of a first heart beat, and Δt2 represents the time of a second heart beat after the first heart beat. The periods Δt1 and Δt2 occur while the heart pump system is at least partially disposed within the patient's heart. Point 310 represents the dicrotic notch of the first heart beat, and point 320 represents the dicrotic notch of the second heart beat. Diastole Δt3 represents the diastole of the second heart beat. During periods Δt1, Δt2, and Δt3, the pump operates at a first pump speed. In some implementations, the pump operates at a second pump speed during the period Δt3. For example, the pump speed can be increased during the period Δt3. At the higher pump speed, the measured aortic pressure and total flow rate are greater compared to the lower pump speed.

[0062] At a given known time t during the diastolic phase Δt 02 In this case, the pressure P(t 02 ) is known, and the second known time t 03 In this case, the pressure P(t 03 ) is known, and a third known time t 04 In this case, the pressure P(t 04 ) is known. At each of these times in diastole Δt3, the pump flow is known from the motor current delivered to the pump motor at that time. Thus, P0, R, and C can be calculated using the following equations:

number

[0063] FIG. 4 illustrates a compliance sensor 410 coupled to a patient 400. The compliance sensor 410 may include various hardware elements configured to perform the methods described herein, as well as additional processes. In some implementations, the compliance sensor includes an intravascular blood pump (e.g., pump 202 of FIG. 1). The intravascular blood pump may be configured to be disposed at least partially within the patient's heart. In some implementations, the intravascular blood pump includes a cannula, an impeller configured to rotate within a blood vessel to pump blood through the cannula, and a drive mechanism configured to provide power to rotate the impeller. In some implementations, the cannula may be configured to extend across the aortic valve such that a distal end of the cannula is in the left ventricle and a proximal end of the cannula is in the aorta. For example, the heart pump system may be considered "in place" when the cannula is positioned across the aortic valve such that a blood inlet to the pump is located in the left ventricle and an outlet from the pump is located in the aorta. The drive mechanism may include an internal motor, a drive cable, a drive shaft, or any other suitable elements, or combinations thereof.

[0064] In some implementations, the compliance sensor 410 includes an elongated catheter body coupled to the cannula. The elongated catheter may include a drive cable, electrical wiring connecting the blood pump to a control system, any suitable element, or any combination thereof. In some implementations, the blood pump includes a pump housing and a motor housing, the motor housing coupled to the cannula at a distal end of the motor housing. An impeller can rotate within the pump housing to cause blood flow to the cannula.

[0065] The compliance sensor 410 includes a pressure sensor configured to detect pressure within a blood vessel resulting at least in part from the pumping of blood within the blood vessel. For example, the pressure sensor can be a differential pressure sensor that is part of a blood pump. One side or surface of the differential pressure sensor can be exposed to aortic pressure and a second side or surface of the differential pressure sensor can be exposed to intraventricular pressure, and the differential pressure sensor can measure the difference between the aortic pressure and the intraventricular pressure. As another example, the pressure sensor 412 can include a pressure measurement lumen configured to measure aortic pressure.

[0066] The compliance sensor 410 includes a controller 414. The controller 414 is connected to the pressure sensor 412. The controller 414 may be directly or indirectly connected to the pressure sensor 412. For example, the controller 414 may be connected to the pressure sensor 412 via electrical wiring, wireless signals, or any other suitable means. The controller 414 is configured to detect a signal from the pressure sensor representative of blood pressure. All or part of the controller 414 may be in a controller unit separate / remote from the intravascular blood pump. In some implementations, the control system is internal to the intravascular blood pump.

[0067] In some implementations, the controller 414 is configured to detect changes in the resistance of the impeller rotation within the blood vessel. For example, the resistance can be calculated at various times based on cardiac pressure and flow measurements, as described above in connection with FIG.

[0068] In some implementations, the controller 414 is configured to maintain a constant impeller rotational speed based on the detected resistance to impeller rotation. The current supplied to the impeller motor can be varied based on the current required to maintain the motor speed. Thus, the motor current can be related to the flow rate through the heart.

[0069] In some implementations, the controller 414 is configured to calculate vascular compliance and vascular resistance based on the change in resistance to impeller rotation using a transfer function. For example, vascular compliance and resistance can be determined as described above in connection with FIG. 3. In another example, while maintaining the pump speed at a constant speed (speed1), a set of measurements of diastolic aortic pressure P1(t) and a set of measurements of pump flow i1(t) are determined for a set of time points (e.g., t is t1, t2, t3, t4, t5, t6, t7, t8, t9, t10, t111, t121, t131, t141, t151, t161, t171, t181, t191, t192, t193, t194, t195, t196, t197, t198, t199, t200, t201, t202, t203, t204, t205, t206, t207, t208, t210, t211, t212, t213, t214, t215, t216, t217, t2181, t2198, t2199, t2207, t22181, t2222, t223, t223, t224, t225, t226, t227, t228, t229, t330, t331, t332, t333, t334, t335, t336, t337, t 01 , t1 02 , t1 03 , etc. The controller can then set the pump to a different constant speed (speed2) and obtain a second set of diastolic aortic pressure measurements P2(t) and a second set of pump flow measurements i2(t) for a second set of time points (e.g., t is equal to t2 01 , t2 02 , t2 03 , etc.) Using the difference between the two sets of pressure measurements P1(t) and P2(t) and the difference between the two sets of pump flows i1(t) and i2(t), the vascular resistance can be calculated by the following formula:

number

[0070] FIG. 5 illustrates a process 500 for determining the total volume of blood pumped per heartbeat. The process 500 can be performed using the heart pump system 100 of FIG. 1 or any other suitable pump. In some implementations, the pump is an intravascular blood pump device that is placed in the patient's heart by percutaneous insertion. In some implementations, the pump can be a surgically implanted device, a left ventricular assist device, a counterpulsation device, an expandable heart pump, or any other suitable device. The pump may be introduced into a patient because the patient is in a state of cardiogenic shock or otherwise facing declining health. The pump can be placed across the aortic valve such that the blood inlet to the pump (e.g., blood inlet 172 of FIG. 1) is located in the left ventricle and the outlet from the pump (e.g., outlet opening 170 of FIG. 1) is located in the aorta. The pump contributes to the operation of the natural heart such that the CO from the heart is equal to the natural CO plus the pump output.

[0071] In step 502, a hemodynamic parameter is monitored while operating the cardiac pump at a first pump speed. The hemodynamic parameter may be any parameter related to the flow of blood in a body organ or tissue. For example, the hemodynamic parameter may be heart rate, blood pressure, arterial oxygen saturation, mixed venous saturation, central venous oxygen saturation, arterial blood pressure, mean arterial pressure, right arterial pressure, central venous pressure, right ventricular pressure, pulmonary artery pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, left atrial pressure, aortic pressure, pressure differential, left ventricular end pressure, stroke volume, stroke volume index, stroke volume variation, systemic vascular resistance, systemic vascular resistance index, pulmonary vascular resistance, pulmonary vascular resistance index, pulmonary vascular resistance, pulmonary vascular resistance index, left ventricular stroke work, The parameters may include at least one of left ventricular stroke work index, right ventricular stroke work, right ventricular stroke work index, coronary artery perfusion pressure, right ventricular end diastolic volume, right ventricular end diastolic volume index, right ventricular end systolic volume, right ventricular ejection fraction, arterial oxygen content, venous oxygen content, arterial-venous oxygen content difference, oxygen delivery, oxygen delivery index, oxygen consumption, oxygen consumption index, oxygen uptake budget, oxygen uptake index, total peripheral resistance, CO, cardiac index, and CPO. The pump speed is the speed of operation of the pump and corresponds to the amount of blood flow provided by the operation of the pump. In some implementations, the pump speed may correspond to the rotational speed of the rotor. For example, the pump speed may be 10,000 RPM, 20,000 RPM, 30,000 RPM, 40,000 RPM, 50,000 RPM, 60,000 RPM, 70,000 RPM, 80,000 RPM, 90,000 RPM, 100,000 RPM, or any suitable speed. The pump speed may correspond to a power level or P level, as described above in connection with FIG. 1. For example, the pump speed may be P-1, P-2, P-3, P-4, P-5, P-6, P-7, P-8, P-9, or any other suitable value. In some implementations, the pump speed may instead correspond to the rate at which the pump's chamber fills with and expels blood.

[0072] In step 504, the diastole of the cardiac cycle is identified based on the shape of the hemodynamic parameters over time. Diastole is the time it takes for the heart to complete diastole, the phase of the cardiac cycle during which the myocardium relaxes and allows the ventricles to fill with blood. For example, the diastole may be 0.05 seconds, 0.1 seconds, 0.2 seconds, 0.3 seconds, 0.4 seconds, 0.5 seconds, 0.6 seconds, 0.7 seconds, 0.8 seconds, 0.9 seconds, 1 second, or any suitable length.

[0073] In step 506, a time-varying relationship between aortic pressure and blood flow during diastole is determined. The time-varying relationship is determined by calculating the time-varying relationship between two current sources i h and i p The model may be a Windkessel model with a resistance R and a compliance C. The governing equation of this model is:

number

number

[0074] In step 508, the total amount of blood pumped per heartbeat, which represents cardiac performance, is calculated based on the time-varying relationship between aortic pressure and blood flow in diastole. For example, once R and C are determined, the CO of the heart can be determined (e.g., as described below with respect to FIG. 7). In some implementations, another index representing cardiac performance can be calculated. For example, the index representing cardiac performance can be ventricular resistance, ventricular compliance, CO, CPO, stroke volume, stroke work, ejection fraction, cardiac index, or patient survival prediction. Many indexes representing cardiac performance are interrelated. For example, CO is determined based on the flow rate of blood through the pump. Stroke volume is an index of left ventricular function, and its formula is SV=CO / HR, where SV is stroke volume, CO is cardiac output, and HR is heart rate. Stroke work is the work done by the ventricle to eject blood and can be calculated from the stroke volume according to the formula SW=SV*MAP, where SW is the stroke work, SV is the stroke volume, and MAP is the mean arterial pressure. Cardiac work is calculated by the product of stroke work and heart rate. CPO is a measure of cardiac function that represents the pumping ability of the heart and is expressed in watts. CPO is calculated using the formula CPO=mAoP*CO / 451, where CPO is the cardiac output, mAoP is the mean arterial pressure, CO is the cardiac output, and 451 is a constant used to convert mmHg x L / min to watts. Ejection fraction can be calculated by dividing the stroke volume by the blood volume of the ventricle. Other parameters such as chamber pressure, preload state, afterload state, cardiac recovery, flow loading state, variable volume loading state, and / or cardiac cycle flow state can be calculated from or determined via these values.

[0075] In some implementations, pump operation is adjusted based on the indicators representative of cardiac performance. Adjustments to pump operation may include increasing pump speed, decreasing pump speed, adjusting pump placement, turning off the pump, or any other suitable adjustment. For example, pump speed may be increased when the total amount of blood being pumped is below a threshold, while pump speed may be decreased when the amount of blood is above a threshold.

[0076] In some implementations, the method includes operating a blood pump within a patient's vascular system and determining a cardiac output of the patient's heart using any of the systems and sensors described above. The pumping speed of the blood pump can be adjusted based on the determined cardiac output.

[0077] FIG. 6 illustrates a process 600 for determining cardiac output. The process 600 can be performed using the heart pump system 100 of FIG. 1 or any other suitable pump. In some implementations, the pump is an intravascular blood pump device that is placed in the patient's heart by percutaneous insertion. The pump may be introduced into the patient because the patient is in a state of cardiogenic shock or otherwise facing declining health. The pump may be placed across the aortic valve such that the blood inlet to the pump (e.g., blood inlet 172 of FIG. 1) is located in the left ventricle and the outlet from the pump (e.g., outlet opening 170 of FIG. 1) is located in the aorta. The pump contributes to the operation of the native heart such that CO from the heart is equal to the native CO plus the pump output.

[0078] In step 602, hemodynamic support is applied to the heart at a first pumping rate. The hemodynamic pumping rate is delivered over multiple heartbeats of the heart. Each heartbeat includes a systolic upstroke, a dicrotic notch, and a diastolic downstroke that occurs after the dicrotic notch. For example, the hemodynamic pumping rate may be provided for 2, 3, 4, 10, 20, 30, 100, 200, or any other suitable number of heartbeats.

[0079] In step 604, a plurality of aortic pressure measurements are detected during the diastolic downstroke in a particular one of the plurality of beats. For example, pressure may be sampled at a rate of 1, 2, 3, 10, 20, 30, 100, 200, 300, 1000, 2000, 3000, or any other suitable number of samples per second. In some examples, the aortic pressure is sampled only during the diastolic downstroke. In some examples, the aortic pressure is measured constantly or periodically. In some examples, the sampling rate of the aortic pressure is changed during the diastolic downstroke.

[0080] In step 606, a first aortic pressure measurement of the plurality of aortic pressure measurements is compared to a second aortic pressure measurement of the plurality of aortic pressure measurements in a time-dependent nonlinear model of the vascular system to determine systemic vascular resistance and compliance. In some implementations, where cardiac output is generated solely by the action of the blood pump, at least one aortic pressure measurement is taken at the end of diastole. For example, as shown in FIG. 3 and described above, pressure can be measured at a series of time points during diastole. For each of these pressure measurements, pressure can be measured and flow can be estimated. Pressure and flow measurements can be compared between two time points in combination with known measurement time points to calculate cardiac parameters such as aortic resistance and compliance.

[0081] In step 608, the cardiac output at the particular beat is determined as a function of the determined systemic vascular resistance and compliance. In some implementations, determining the cardiac output includes determining cardiac outputs for a plurality of particular beats of the plurality of beats and applying at least one of a sum, an average, or a linear regression to the determined cardiac outputs to determine a cumulative indicator of cardiac output. The cumulative indicator of cardiac output can be indicative of cardiac performance or overall patient health.

[0082] FIG. 7 shows two plots for the same 10 second period, one for aortic pressure and one for cardiac blood flow. The y-axis of the upper plot represents aortic pressure (mmHg) while the x-axis represents time (sec). The y-axis of the lower plot represents calculated total cardiac blood flow (liters / min) while the x-axis represents time (sec). In this example, systemic vascular resistance R and compliance C are known. For example, R and C can be calculated using measurements of aortic pressure taken over the illustrated 10 second period in combination with pump data as described above. Total cardiac blood flow i h +i p is expressed as (1)

number

[0083] The foregoing is merely illustrative of the principles of the present disclosure, and the device may be embodied in other aspects than those described above, which are presented for purposes of illustration and not limitation. It should be understood that while the device disclosed herein is shown as being used in percutaneous insertion of a heart pump, it is applicable to devices for other applications requiring hemostasis.

[0084] Those skilled in the art will appreciate that changes and modifications may occur to those skilled in the art upon consideration of this disclosure. The disclosed features may be implemented in any combination and subcombination (including multiple dependent combinations and subcombinations) with one or more other features described herein. The various features described or illustrated above, including any components thereof, may be combined or integrated into other systems. Furthermore, certain features may be omitted or not implemented.

[0085] The above-mentioned systems and methods may be implemented locally on the heart pump system or on a controller of the heart pump system, such as an AIC. The heart pump system may include a data processing device. The systems and methods described herein may be performed remotely on a separate data processing device. The separate data processing device may be directly or indirectly connected to the heart pump system via a cloud application. The heart pump system may communicate with the separate data processing device in real time (or near real time).

[0086] In general, aspects of the subject matter and functional operations described herein can be implemented in digital electronic circuitry, or computer software, firmware, or hardware, including structures disclosed herein and their structural equivalents, or a combination of one or more of them. Aspects of the subject matter described herein can be implemented as one or more computer program products, i.e., one or more modules of computer program instructions encoded on a computer-readable medium for execution by or control of the operation of a data processing device. The computer-readable medium can be a machine-readable storage device, a machine-readable storage substrate, a memory device, a composition affecting a machine-readable propagated signal, or a combination of one or more of them. The term "data processing apparatus" encompasses all apparatus, devices, and machines for processing data, such as, for example, a programmable processor, a computer, or multiple processors or computers. In addition to hardware, an apparatus can include code that creates an execution environment for a given computer program, such as, for example, code that constitutes a processor firmware, a protocol stack, a database management system, an operating system, or one or more combinations of them. A propagated signal is an artificially generated signal, such as a machine-generated electrical, optical, or electromagnetic signal generated to encode information for transmission to an appropriate receiver apparatus.

[0087] A computer program (also known as a program, software, software application, script, or code) can be written in any form of programming language, including compiled or interpreted languages, and can be deployed in any form, for example as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program may correspond to a file in a file system. A program can be stored as part of a file that holds other programs or data (e.g., one or more scripts stored in a markup language document), in a single file dedicated to that program, or in multiple cooperating files (e.g., a file that stores one or more modules, subprograms, or portions of code). A computer program can be deployed to be executed on one computer, or on multiple computers located at one site or distributed across multiple sites and interconnected by a communications network.

[0088] The processes and logic flows described herein may be performed by one or more programmable processors executing one or more computer programs to perform functions by manipulating input data to generate output. The processes and logic flows may also be performed by, and an apparatus may be implemented as, special purpose logic circuitry, such as, for example, an FPGA (field programmable gate array) or an ASIC (application specific integrated circuit).

[0089] Processors suitable for executing a computer program include, for example, both general purpose and special purpose microprocessors, and any one or more processors of any kind of digital computer. Typically, a processor receives instructions and data from a read-only memory or a random access memory or both. The essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Typically, a computer further includes one or more mass storage devices for storing data, such as, for example, magnetic disks, magneto-optical disks, or optical disks, or is operatively coupled to such mass storage devices for receiving data, transferring data, or both. However, a computer need not necessarily have such devices.

[0090] Examples of changes, substitutions, and modifications are ascertainable to those skilled in the art and can be made without departing from the scope of the information disclosed herein. All references cited herein are incorporated by reference in their entirety and form part of this application.

Claims

1. A method for determining cardiac output, comprising the steps of: applying hemodynamic support to the heart with a blood pump, the hemodynamic support including pumping blood at a first pumping rate for a plurality of beats of the heart, each beat including a systolic upstroke, a dicrotic notch, and a diastolic downstroke occurring after the dicrotic notch; detecting a first aortic pressure measurement at a first time point and a second aortic pressure measurement at a second time point, the first time point and the second time point occurring during the diastolic downstroke of a particular one of the plurality of beats; determining a first blood flow rate pumped by the blood pump at the first time point and a second blood flow rate pumped by the blood pump at the second time point; Determining cardiac output based on the first aortic pressure measurement, the second aortic pressure measurement, the first blood flow, and the second blood flow.

2. calculating a time-dependent nonlinear model of the vascular system using the first aortic pressure measurement, the second aortic pressure measurement, the first blood flow, and the second blood flow to determine systemic vascular resistance and compliance; determining cardiac output at the particular beat based on the determined systemic vascular resistance and compliance; 2. The method of claim 1, further comprising:

3. The method of claim 2 , wherein the time-dependent nonlinear model is a Windkessel model.

4. 2. The method of claim 1, further comprising determining a first cumulative indicator of cardiac output of the heart.

5. 2. The method of claim 1, wherein the step of determining the cardiac output comprises determining a first plurality of cardiac output values, each cardiac output value of the first plurality of cardiac output values ​​corresponding to a respective beat of a first set of beats of the plurality of beats.

6. comparing a first cardiac output value to a second cardiac output value, the first plurality of cardiac output values ​​including the first cardiac output value and the second cardiac output value; determining a change in cardiac performance of the heart based on a comparison between the first cardiac output value and the second cardiac output value; varying hemodynamic support to the patient based on the determined change in cardiac performance of the heart over time.

6. The method of claim 5, further comprising:

7. 6. The method of claim 5, further comprising applying at least one of a sum, an average, or a linear regression to the determined cardiac output values ​​to calculate a first cumulative indicator of cardiac output of the heart.

8. 8. The method of claim 7, wherein the first cumulative indicator of cardiac output of the heart is indicative of cardiac performance of the heart.

9. determining a second cumulative indicator of cardiac output of the heart for a second set of beats of the plurality of beats, the second set of beats occurring after the first set of beats; comparing the first cumulative indicator of cardiac output to a second cumulative indicator of cardiac output; determining (i) an improvement in cardiac performance of the heart or (ii) a decrease in cardiac performance of the heart based on a comparison between the first cumulative indicator and the second cumulative indicator; modifying hemodynamic support to the patient based on the determined improvement or deterioration of cardiac performance of the heart over time.

9. The method of claim 8, further comprising:

10. The step of determining the second cumulative indicator comprises: determining a second plurality of cardiac output values, each cardiac output value of the second plurality of cardiac output values ​​corresponding to a respective beat of the second set of beats; applying at least one of a sum, an average, or a linear regression to the determined cardiac output values ​​to calculate a second cumulative indicator of cardiac output of the heart; 10. The method of claim 9, comprising:

11. The step of determining cardiac output of the particular beat comprises: detecting a plurality of aortic pressure measurements at a plurality of time points during the diastolic downstroke of the particular beat, each aortic pressure measurement of the plurality of aortic pressure measurements corresponding to a point in the plurality of time points; determining a plurality of blood flow rates pumped by the blood pump at the plurality of time points; calculating a plurality of time-dependent nonlinear models of the vascular system using the plurality of aortic pressure measurements and the plurality of blood flow rates to determine a plurality of systemic vascular resistance and compliance values; determining a plurality of cardiac output values ​​for the particular beat based on the determined plurality of systemic vascular resistance and compliance values; applying at least one of a sum, an average, or a linear regression to the determined cardiac output values ​​to calculate the cardiac output for the particular beat; The method of any one of claims 1 to 10, comprising:

12. determining a second cumulative indicator of cardiac output for a second beat of the plurality of beats, the second beat occurring after the particular beat; and comparing the first cumulative indicator of cardiac output to a second cumulative indicator of cardiac output; determining (i) an improvement in cardiac performance of the heart or (ii) a decrease in cardiac performance of the heart based on a comparison between the first cumulative indicator and the second cumulative indicator; modifying the applied hemodynamic support based on a determination that the cardiac performance of the heart is improving or declining over time; 12. The method of claim 11, further comprising:

13. 13. The method of any one of claims 1 to 12, wherein the hemodynamic support is provided by an intracardiac blood pump having a cannula configured to be placed within a ventricle of the heart.

14. The method of claim 13 , wherein the cannula is configured for placement within the left ventricle.

15. 15. The method of claim 13, wherein a pressure sensor is provided with the intra-cardiac blood pump, and wherein detecting the plurality of aortic pressure measurements comprises measuring an aortic pressure with the pressure sensor.

16. 16. The method of claim 15, wherein the pressure sensor is disposed within a housing of the blood pump.

17. 17. The method of claim 13, wherein detecting the plurality of aortic pressure measurements comprises receiving the aortic pressure measurements from a pressure sensor remote from the intra-cardiac blood pump.

18. 18. The method of any one of claims 13 to 17, wherein operation of the intracardiac blood pump is regulated by a controller, the controller comprising a memory that stores the time-dependent nonlinear model of the vascular system.

19. 19. The method of any one of claims 1 to 18, further comprising adjusting hemodynamic support applied to the heart based on said determined cardiac output.

20. 20. The method of any one of claims 1 to 19, further comprising configuring the determined cardiac output for display.

21. 21. The method of any one of claims 1 to 20, wherein the systemic vascular resistance and compliance represent the resistance and compliance of the aorta.

22. 22. The method of any one of claims 1 to 21, wherein determining cardiac output comprises averaging total cardiac blood flow over a period of time.

23. The method of any one of claims 1 to 22, wherein the period is the length of the particular beat.

24. A method for determining cardiac performance of a heart, comprising the steps of: monitoring hemodynamic parameters during operation of the mechanical circulatory assist device at the first device operating parameters; identifying a diastolic phase of a cardiac cycle based on the shape of the hemodynamic parameter over time; establishing a time-varying relationship between aortic pressure and blood flow during diastole; Calculating the total amount of blood induced by the mechanical circulatory assist device per heart beat based on the time-varying relationship between aortic pressure and blood flow during diastole, to indicate cardiac performance.

25. 25. The method of claim 24, wherein the mechanical circulatory assist device is an intravascular blood pump and the monitoring occurs while operating the pump at a first pump speed.

26. The method according to any one of claims 24 to 25, wherein the hemodynamic parameter is aortic pressure.

27. Calculating the total amount of blood pumped per heartbeat determining vascular compliance and vascular resistance of the systemic vasculature based on a mathematical representation of the hemodynamic parameters over time; calculating the stroke volume of the systemic vasculature using the determined vascular compliance and vascular resistance; The method of any one of claims 24 to 26, comprising:

28. a system for generating blood flow in a patient's blood vessel, the system comprising a motor and an impeller; Detects changes in the resistance of the impeller rotation within the blood vessel, maintaining a constant impeller rotational speed based on the detected resistance to impeller rotation; Calculating vascular compliance and vascular resistance using a transfer function based on the change in resistance to the impeller rotation. With a controller configured like this: A vascular sensor comprising:

29. 30. The vascular sensor of claim 28, wherein the transfer function is a Windkessel model.

30. 30. The vascular sensor of claim 28 or 29, wherein the controller is configured to determine an index representative of cardiac performance based on the vascular compliance and the vascular resistance.

31. 32. The vascular sensor of claim 31, wherein the index representative of cardiac performance is at least one of cardiac output, cardiac power, stroke volume, stroke work, ejection fraction, cardiac contractility, ventricular elastance, cardiac index, or patient survival prediction.

32. The vascular sensor of claim 30 , wherein the controller is configured to adjust the impeller rotational speed based on at least one of the vascular resistance, the vascular compliance, or the cardiac output.

33. The controller: receiving measurements representative of aortic pressure over a period of time; Detecting the current delivered to the pump; and determining the amount of blood pumped by the system over the period based on the current delivered to the pump; It is configured as follows: The vascular sensor of any one of claims 28 to 32, wherein the calculation of the vascular compliance and the vascular resistance is further based on measurements representative of the aortic pressure and the blood flow.

34. The vascular sensor of any one of claims 28 to 33, wherein the system for generating blood flow in the patient's blood vessel comprises a cannula configured to extend into a left ventricle of the heart, and a pressure sensor configured to detect at least one of an aortic pressure, a left ventricular pressure, or a differential pressure.

35. The vascular sensor of any one of claims 28 to 34, wherein the system for generating blood flow in the patient's blood vessel is an intracardiac blood pump incorporating an impeller within a shroud.

36. A system for generating blood flow within a blood vessel of a patient; a hemodynamic sensor configured to detect a change in a hemodynamic parameter due to the induced blood flow; a controller configured to receive the sensor signal and calculate the resistance of the blood vessel as a function of blood flow in the blood vessel and aortic pressure; A vascular sensor comprising:

37. The system includes a motor and an impeller, and the controller includes: Detects changes in the resistance of the impeller rotation within the blood vessel, maintaining a constant impeller rotational speed based on the detected resistance to impeller rotation; and Transmitting pump operation data to a computing device 37. The sensor of claim 36, configured as follows:

38. The vascular sensor of any one of claims 36 to 37, wherein the pump operation data includes at least one of pressure measurements, current measurements, changes in resistance to impeller rotation, and estimates of flow rate.

39. The controller: receiving a first aortic pressure measurement corresponding to a first time point and a second aortic pressure measurement corresponding to a second time point, wherein the first time point and the second time point are in the diastolic downstroke of the heart rate; determining a first blood flow rate pumped by the blood pump at the first time and a second blood flow rate pumped by the blood pump at the second time; and (i) the first aortic pressure measurement, (ii) the second aortic pressure measurement, (iii) the first blood flow rate, and (iv) the second blood flow rate are used to calculate a time-dependent nonlinear model of the vascular system to determine systemic vascular resistance and compliance. The vascular sensor of any one of claims 36 to 38, configured as follows:

40. 40. The vascular sensor of claim 39, wherein the time-dependent nonlinear model is a Windkessel model.

41. The vascular sensor of any one of claims 36 to 40, wherein the controller is further configured to determine cardiac output based on the first aortic pressure measurement, the second aortic pressure measurement, the first blood flow rate, and the second blood flow rate.

42. The vascular sensor of any one of claims 36 to 41, wherein the controller is configured to receive pump operation commands from the computing device, the pump operation commands being based on the pump operation data.

43. A method for providing mechanical circulatory support to a patient using a blood pump, comprising the steps of: operating a blood pump within a patient's vascular system; determining the cardiac output of the patient's heart using any one of claims 1 to 42; Adjusting the speed of the blood pump based on the determined cardiac output.

44. an intracardiac blood pump having a cannula configured to extend into a left ventricle of the heart; and a pressure sensor configured to detect aortic pressure; 4. The method of claim 3, further comprising: determining cardiac output or vascular resistance according to any of the methods of the preceding claims. Mechanical circulatory support systems.

45. 40. The system of claim 38, wherein the pressure sensor is a vascular sensor as described in claim 36.

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