Patent Publication Number: US-2021193315-A1

Title: Systems and methods for personalized cardiovascular analyses

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims priority to provisional application Ser. No. 62/951,312, filed Dec. 20, 2019, which is incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE DISCLOSURE 
     This disclosure relates to monitoring patients with cardiovascular issues, and more particularly, this disclosure relates to executing patient-specific cardiovascular analyses. 
     BACKGROUND 
     Ventricular assist systems (VASs) may include ventricular assist devices (VADs), such as implantable blood pumps used for both short-term (i.e., days, months) and long-term (i.e., years or a lifetime) applications where a patient&#39;s heart is incapable of providing adequate circulation, commonly referred to as heart failure or congestive heart failure. A patient suffering from heart failure may use a VAS while awaiting a heart transplant or as a long-term destination therapy. In another example, a patient may use a VAS while recovering from heart surgery. Thus, a VAS can supplement a weak heart (i.e., partial support) or can effectively replace the natural heart&#39;s function. VASs can be implanted in the patient&#39;s body and powered by an electrical power source inside or outside the patient&#39;s body. 
     Understanding and managing the hemodynamic state of a heart failure patient may be relatively challenging. Further, additional complexity arises for VAD patients with one or more underlying conditions, such as right ventricle (RV) dysfunction, valve disorders, arrhythmias, etc. 
     One focus of next-generation VAD development is adding system enhancements to assist physicians in optimizing therapy to improve adverse event profiles and overall patient quality of life. Example enhancements include using improved sensing abilities (e.g., flow waveform sensing, pressure waveform sensing, accelerometers, etc.) in conjunction with closed loop control algorithms (e.g., pulsing and physiologic control). These enhancements may be utilized in so-called “Smart VADs”. 
     However, with these new capabilities comes an increase in complexity and sophistication of patient management, particularly if a patient has additional devices, such as pacemakers or pulmonary artery (PA) pressure sensors. Thus, there is a need to educate and train physicians regarding how to manage complex patient/device system interactions, and to understand the meaning of new diagnostic tools as they come on line. Further, there is a need to simplify and consolidate cardiac assist device interfaces, to leverage remote monitoring to record patient/device data outside the clinic for extended periods, and to develop algorithms that can process and interpret device data to facilitate optimizing patient treatment. Accordingly, there is a need for a unified remote monitoring infrastructure. 
     BRIEF SUMMARY OF THE DISCLOSURE 
     In one embodiment, the present disclosure is directed to a method for performing personalized cardiovascular analyses. The method includes building, using a modeling and simulation computing device, a patient-specific model, storing, using the modeling and simulation computing device, the patient-specific model in a database, receiving, at the modeling and simulation computing device, remote monitoring data from at least one remote monitoring data source, and receiving, at the modeling and simulation computing device, clinical data from at least one clinical data source. The method further includes updating, using the modeling and simulation computing device, the patient-specific model using the remote monitoring data and the clinical data, performing, using the modeling and simulation computing device, at least one simulation on the updated patient-specific model, and outputting, from the modeling and simulation computing device, at least one output based on the at least one simulation. 
     In another embodiment, the present disclosure is directed to a computing device for performing personalized cardiovascular analyses. The computing device includes a memory device and a processor communicatively coupled to the memory device. The processor is configured to build a patient-specific model, store the patient-specific model in the memory device, receive remote monitoring data from at least one remote monitoring data source, receive clinical data from at least one clinical data source, update the patient-specific model using the remote monitoring data and the clinical data, perform at least one simulation on the updated patient-specific model, and output an output based on the at least one simulation. 
     In yet another embodiment, the present disclosure is directed to non-transitory computer-readable media having computer-executable instructions thereon. When executed by a processor of a computing device, the instructions cause the processor of the computing device to build a patient-specific model, store the patient-specific model in a database, receive remote monitoring data from at least one remote monitoring data source, receive clinical data from at least one clinical data source, update the patient-specific model using the remote monitoring data and the clinical data, perform at least one simulation on the updated patient-specific model, and output an output based on the at least one simulation. 
     The foregoing and other aspects, features, details, utilities and advantages of the present disclosure will be apparent from reading the following description and claims, and from reviewing the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic diagram of one embodiment of a remote monitoring and simulation system. 
         FIG. 2  is a block diagram of one embodiment of a computing device that may be used to implement the systems and methods described herein. 
         FIG. 3  is a block diagram of a method of performing personalized cardiovascular analyses. 
     
    
    
     Corresponding reference characters indicate corresponding parts throughout the several views of the drawings. 
     DETAILED DESCRIPTION OF THE DISCLOSURE 
     The disclosure provides systems and methods for performing personalized cardiovascular analyses. A method includes building, using a modeling and simulation computing device, a patient-specific model, storing, using the modeling and simulation computing device, the patient-specific model in a database, receiving, at the modeling and simulation computing device, remote monitoring data from at least one remote monitoring data source, and receiving, at the modeling and simulation computing device, clinical data from at least one clinical data source. The method further includes updating, using the modeling and simulation computing device, the patient-specific model using the remote monitoring data and the clinical data, performing, using the modeling and simulation computing device, at least one simulation on the updated patient-specific model, and outputting, from the modeling and simulation computing device, at least one output based on the at least one simulation. 
     The embodiments described herein provide a cloud-based remote monitoring and simulation system that stores and maintains a patient-specific numerical cardiovascular model. The system uses machine learning and optimization techniques to continually update simulation parameters for the model using actual patient data collected from clinical data sources and remote monitoring data sources. The more data collected by the system, the more accurate the model. Because the model replicates a particular patient, the model may also be referred to as a “digital clone” of the particular patient. 
     Referring now to the drawings wherein like reference numerals are used to identify identical components in the various views,  FIG. 1  illustrates one embodiment of a remote monitoring and simulation system  100 . System  100  includes a modeling and simulation computing device  102 . In the exemplary embodiment, modeling and simulation computing device  102  is a cloud-based server system. Alternatively, modeling and simulation computing device  102  may be any computing device suitable for implementing the systems and methods described herein. 
     Modeling and simulation computing device  102  is communicatively coupled to a plurality of remote monitoring data sources  104  and a plurality of clinical data sources  106 . To build and update a patient-specific model for a particular patient, modeling and simulation computing device  102  collects remote monitoring data associated with the patient from remote monitoring data sources  104  and clinical data associated with the patient from clinical data sources  106 , as described herein. In some embodiments, the data may be time-stamped as it is received by modeling and simulation computing device  102 . 
     Remote monitoring data sources  104  associated with the patient may include, for example, a patient monitoring device  110 , a heart failure monitor  112 , a cardiac resynchronization therapy (CRT) device  114 , and a VAD  116 . In some embodiments, patient monitoring device  110  initially collects remote data from other devices (e.g., heart failure monitor  112 , CRT device  114 , and VAD  116 ) and relays that remote monitoring data to modeling and simulation computing device  102 . Alternatively, each device may independently transmit remote monitoring data to modeling and simulation computing device  102 . 
     Remote monitoring data collected from remote monitoring data sources  104  may include patient hemodynamic data and device status data. For example, collected data may include pump flow waveforms, left ventricular (LV) pressure wave forms, and aortic pressure wave forms (e.g., from VAD  116 ). Also, collected remote monitoring data may additionally or alternatively include pulmonary artery (PA) pressure waveforms (e.g., from heart failure monitor  112 ), CRT data (e.g., from CRT device  114 ), and implantable cardiac monitor data. Those of skill in the art will appreciate that other types of remote monitoring data may also be collected. 
     Clinical data sources  106  may include, for example, a physician computing device, an electronic medical record system, etc. Further, clinical data for the patient may include, for example, in clinic measurements, such as right catheter measurements, echocardiogram data, blood pressure measurements, etc. 
       FIG. 2  illustrates one embodiment of a computing device  200  that may be used to implement the systems and methods described herein. Computing device  200  may be used, for example, to implement modeling and simulation computing device  102  (shown in  FIG. 1 ). Computing device  200  includes at least one memory device  210  and a processor  215  that is coupled to memory device  210  for executing instructions. In some embodiments, executable instructions are stored in memory device  210 . In this embodiment, computing device  200  performs one or more operations described herein by programming processor  215 . For example, processor  215  may be programmed by encoding an operation as one or more executable instructions and by providing the executable instructions in memory device  210 . 
     Processor  215  may include one or more processing units (e.g., in a multi-core configuration). Further, processor  215  may be implemented using one or more heterogeneous processor systems in which a main processor is present with secondary processors on a single chip. In another illustrative example, processor  215  may be a symmetric multi-processor system containing multiple processors of the same type. Further, processor  215  may be implemented using any suitable programmable circuit including one or more systems and microcontrollers, microprocessors, reduced instruction set circuits (RISC), application specific integrated circuits (ASIC), programmable logic circuits, field programmable gate arrays (FPGA), and any other circuit capable of executing the functions described herein. 
     In this embodiment, memory device  210  is one or more devices that enable information such as executable instructions and/or other data to be stored and retrieved. Memory device  210  may include one or more computer readable media, such as, without limitation, dynamic random access memory (DRAM), static random access memory (SRAM), a solid state disk, and/or a hard disk. Memory device  210  may be configured to store, without limitation, application source code, application object code, source code portions of interest, object code portions of interest, configuration data, execution events and/or any other type of data. 
     In this embodiment, computing device  200  includes a presentation interface  220  that is coupled to processor  215 . Presentation interface  220  presents information to a user  225 . For example, presentation interface  220  may include a display adapter (not shown) that may be coupled to a display device, such as a cathode ray tube, a liquid crystal display (LCD), an organic LED (OLED) display, and/or an “electronic ink” display. In some embodiments, presentation interface  220  includes one or more display devices. Input signals and/or filtered signals processed using the embodiments described herein may be displayed on presentation interface  220 . 
     In this embodiment, computing device  200  includes a user input interface  235 . User input interface  235  is coupled to processor  215  and receives input from user  225 . User input interface  235  may include, for example, a keyboard, a pointing device, a mouse, a stylus, a touch sensitive panel (e.g., a touch pad or a touch screen), a gyroscope, an accelerometer, a position detector, and/or an audio user input interface. A single component, such as a touch screen, may function as both a display device of presentation interface  220  and user input interface  235 . 
     Computing device  200 , in this embodiment, includes a communication interface  240  coupled to processor  215 . Communication interface  240  communicates with one or more remote devices. To communicate with remote devices, communication interface  240  may include, for example, a wired network adapter, a wireless network adapter, and/or a mobile telecommunications adapter. 
     Referring back to  FIG. 1 , using the remote monitoring data collected from remote monitoring data sources  104  and the clinical data connected from clinical data sources  106 , modeling and simulation computing device  102  builds and updates a patient-specific model. The patient-specific model may be stored, for example, in memory device  210  (shown in  FIG. 2 ). 
     Subsequently, modeling and simulation computing device  102  runs one or more simulations on the patient-specific model to facilitate optimizing patient treatment. Outputs of the simulations may be displayed, for example, on presentation interface  220  (shown in  FIG. 2 ). 
     For example, prior to implanting a VAD in the patient, simulations may be run to simulate how the patient would respond to VAD therapy. In this scenario, the patient model may be built using data from heart failure monitor  112  and/or CRT device  114  and data from in-clinic measurements, as a VAD has not yet been implanted. These results of these simulations may aid the clinician in determining whether or not to implant a VAD, and determining which type of VAD to implant (e.g., LVAD, Bi-VAD, etc.). 
     After implantation of a VAD, simulations may be run on the patient specific-model to simulate operation of the VAD. For example, the impact of adjusting pump speed and/or adjusting pulse type may be simulated. In another example, the impact of adjusting medications and/or fluid volume may be simulated. 
     Further, in some embodiments, modeling and simulation computing device  102  analyzes the patient-specific model (e.g., using machine learning and/or other artificial intelligence techniques). The outputs of these analyses may be displayed, for example, on presentation interface  220  (shown in  FIG. 2 ). 
     For example, as a result of analyzing the patient-specific model, modeling and simulation computing device  102  may recommend changes to VAD parameters (e.g., pump speed) and/or medication to achieve desirable hemodynamic results (e.g., a desired LV pressure profile). In another example, modeling and simulation computing device  102  may track changes in hemodynamic properties over time to identify patterns and/or generate alerts. Tracked hemodynamic properties may include LV/RV systolic function, pulmonary and systemic vascular resistance, vessel compliance, fluid/volume status, valve functionality, hematocrit values, etc. In one example, modeling and simulation computing device  102  tracks cardiac recovery (e.g., ventricle function capacity) and optimizes recovery protocols on a patient-specific basis (e.g., by recommending medication dose/timing, pump weaning, pulse types, etc.). 
     In addition, based on analysis of the patient-specific model, modeling and simulation computing device  102  may generate recommended device settings. For example, modeling and simulation computing device  102  may generate recommended settings for pump speed, physiologic control settings, pulse type, and/or pacemaker settings. In some embodiments, modeling and simulation computing device  102  may control one or more of remote monitoring data sources  104 . For example, modeling and simulation computing device  102  may generate and transmit control signals to CRT device  114  and/or VAD  116  that instruct CRT device  114  and/or VAD  116  to adjust their settings. 
     In the embodiments, described herein, the patient-specific model is an online numerical model that continually updates to match the patient&#39;s current condition based on data received from remote monitoring data sources  104  and clinical data sources  106 . The more data available to and incorporated into the model, the more accurate the simulations and analysis performed by modeling and simulation computing device  102 . 
     The patient-specific model may be, for example, a high fidelity lumped parameter numerical model that simulates a human circulatory system. Further, the model may include features that allow the model to better match actual patients, such as physiologic feedback mechanisms and non-linear outflow graft dynamics. 
     For example, in one embodiment, the model includes approximately seventy-five parameters that define the behavior of the entire circulatory system. By varying these parameters, the model can replicate the behavior of most patients (excluding sever autoregulation disorders). 
     Given the variability of VAD patient properties and hemodynamics, in some embodiments, the model is tuned to match a specific patient. Specifically, machine learning and/or other artificial intelligence techniques are used to systematically vary key model parameters until the simulated model replicates actual hemodynamic and pump parameter data (e.g., ventricle dimensions, PA pressures, etc.) from clinical data. 
     In some embodiments, modeling and simulation computing device  102  also builds a database of generalized models. For example, each generalized model may be built using corresponding clinical study data. The generated database thus includes a plurality of anonymized models. These models may be searchable, for example, based on generic patient properties such as gender, race, weight, BMI, cardiac index, INTERMACS classification, etc. This searchable database allows a user to search for an anonymized model based on properties of a patient of interest, and use that anonymized model as a “starting point” for the patient specific model. Notably, the more similar to the anonymized model to the patient of interest, the faster the anonymized model will converge to an accurate patient-specific model. Further, in some embodiments, modeling and simulation computing device  102  receives existing clinical and/or demographic data associated with the patient, and automatically selects an anonymized model from the database based on the existing clinical and/or demographic data. 
     Using modeling and simulation computing device  102 , a user (e.g., a clinician) is able to clearly visualize and understand the mechanisms behind various patient/device interactions. Further, by running simulations, the user can “virtually” experiment with changing pump speed, medication, fluid volume, etc., and observe the quantified expected hemodynamic response. Further, using modeling and simulation computing device  102 , the user can simulate various events (e.g., dehydration, arrhythmia, exercise, acute hypertension, etc.) to observe the expected outcome and assist in future recognition of such events. 
     Modeling and simulation computing device  102  also continually updates key model parameters (e.g., ventricle elastance curves, valve resistance, aortic compliance, etc.) using machine learning and/or other artificial intelligence techniques to ensure that simulation results match or closely track clinical data. That is, the patient-specific model estimates various patient parameters without a direct physical measurement, which is highly useful for tracking physiological changes over time such as ventricle function, valve leakage, etc. 
     To demonstrate the efficacy of the systems and methods described herein, an example case study will now be described. Specifically, the following case study illustrates how the systems and methods described herein could be used to aid in the treatment of a dilated cardiomyopathy (DCM) heart failure patient through the continuum of heart failure. Those of skill will appreciate that similar techniques could be applied to other heart failure patients as well. This case study is purely fictional, and is intended to demonstrate how the systems and methods described herein could be implemented. 
     In this example, assume a patient gradually develops an underlying electrophysiological disorder (e.g., left bundle branch block) resulting in deteriorating LV functionality. The patient is initially asymptomatic and unaware of any problems. However, over time, electrical conduction issues worsen, ventricular pumping function becomes compromised, and the patient occasionally shows minor heart failure (HF) symptoms (i.e., stage II). 
     Despite activation of the renin-angiotensin (RAS) feedback system, the patient is unable to maintain sufficient cardiac output and arterial pressure. Chronically high ventricular pressures cause the LV to become further dilated, further compromising pumping function. The patient is now symptomatic to the point where they see a cardiologist (i.e., stage III). The cardiologist performs a full hemodynamic workup, measures an ejection fraction of 30%, and identifies the underlying left bundle branch block disorder. 
     At this point, the patient is implanted with a pacemaker and a heart failure monitor (e.g., a PA pressure sensor), and assigned a typical HF medication regiment. The patient is then registered with an account for a remote monitoring system (which may be the same as or separate from modeling and simulation computing device  102 ) and given required equipment to enable remote monitoring of the devices. Further, in accordance with the systems and methods described herein, the clinician uses modeling and simulation computing device  102  to initialize a patient-specific model for the patient. For example, modeling and simulation computing device  102  may automatically select initial parameters for the model based on existing clinical and/or demographic data for the patient. 
     The pacemaker initially improves cardiac pumping capacity and alleviates HF systems visible to the patient, returning to stage II. However, prior chronic LV dilation has caused the heart to become mechanically compromised and high ventricular filling pressures persist. Over the following months/years, the LV continues to dilate despite successful pacing. The heart failure monitor tracks PA pressures drifting higher, and these results are passed to the remote monitoring system and are visible to the clinician. Further, the patient-specific model has been updating based on data received from the pacemaker and heart failure monitor, and now has a matching confidence level to the actual patient of 65%. Modeling and simulation computing device  102  is also reporting, based on analysis of the model, reduced LV systolic function. 
     The clinician decides to have the patient return to the clinic to receive a full hemodynamic workup despite generally feeling okay. Results indicate a severely dilated LV and poor general hemodynamics. These in-clinic results are provided to modeling and simulation computing device  102 , and the matching confidence level increases to 75%. The clinician adjusts medication and sends the patient home for remote observation. 
     Over the next few months, HF symptoms worsen to stage IV, and the patient is unable to perform daily tasks. The patient-specific model suggests very low, and steadily worsening, LV systolic function. Eventually the patient returns to the clinic for another hemodynamic workup. Results are poor, with an ejection fraction of 20% and low cardiac index. The patient appears to be a good recovery candidate (younger with only a couple of years in HF), but a poor transplant candidate (blood type O, weighing over 100 kilograms). 
     Using modeling and simulation computing device  102 , the clinician simulates how the patient would respond to VAD therapy (the matching confidence level is now 80%). The patient-specific model indicates a favorable hemodynamic response to VAD support and strong RV function. Accordingly, the decision is made to implant a VAD capable of communicating data to modeling and simulation computing device  102 . 
     Within weeks after the VAD implantation, the patient is healthy and walking around with no HF symptoms (i.e., stage I). The patient-specific model, which is now also incorporating an abundance of data from the VAD, has now reached a matching confidence level of 95%. After three months, analysis of the patient-specific model by the modeling and simulation computing device  102  is now indicating improved LV systolic function and remodeling. The clinician reviews the logged data and allows the modeling and simulation computing device  102  to instruct the VAD to initiate a recovery protocol, in which the VAD periodically reduces pump speed to automatically “train” the LV. 
     After another two months, analysis of the patient-specific model by the modeling and simulation computing device  102  indicates consistently strong LV function, and the weaning algorithms have been implemented to reduce VAD pump speed to relatively low levels such that VAD support is minimal. Using modeling and simulation computing device  102 , the clinician simulates removal of the VAD, and the results of the simulation indicate a high probability of recovery. Thus, the decision is made to explant the VAD. Two years after explanting the VAD, the patient shows stable durable recovery. The patient-specific model maintained by modeling and simulation computing device  102  is still active using available data from the pacemaker and heart failure monitor. 
     Accordingly, this case study demonstrates the advantages realized using the systems and methods described herein. 
       FIG. 3  is a block diagram of a method  300  of performing personalized cardiovascular analyses. Method  300  may be implemented, for example, by modeling and simulation computing device  102  (shown in  FIG. 1 ). 
     Method  300  includes building  302  a patient-specific model. Method  300  further includes storing  304  the patient-specific model in a database. In addition, method  300  includes receiving  306  remote monitoring data from at least one remote monitoring data source, and receiving  308  clinical data from at least one clinical data source. Method  300  further includes updating  310  the patient-specific model using the remote monitoring data and the clinical data. Further, method  300  includes performing  312  at least one simulation on the updated patient-specific model and outputting  314  at least one output based on the at least one simulation. 
     The systems and methods described herein include building, using a modeling and simulation computing device, a patient-specific model, storing, using the modeling and simulation computing device, the patient-specific model in a database, receiving, at the modeling and simulation computing device, remote monitoring data from at least one remote monitoring data source, and receiving, at the modeling and simulation computing device, clinical data from at least one clinical data source. The systems and methods further include updating, using the modeling and simulation computing device, the patient-specific model using the remote monitoring data and the clinical data, performing, using the modeling and simulation computing device, at least one simulation on the updated patient-specific model, and outputting, from the modeling and simulation computing device, at least one output based on the at least one simulation. 
     Although certain embodiments of this disclosure have been described above with a certain degree of particularity, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this disclosure. All directional references (e.g., upper, lower, upward, downward, left, right, leftward, rightward, top, bottom, above, below, vertical, horizontal, clockwise, and counterclockwise) are only used for identification purposes to aid the reader&#39;s understanding of the present disclosure, and do not create limitations, particularly as to the position, orientation, or use of the disclosure. Joinder references (e.g., attached, coupled, connected, and the like) are to be construed broadly and may include intermediate members between a connection of elements and relative movement between elements. As such, joinder references do not necessarily infer that two elements are directly connected and in fixed relation to each other. It is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative only and not limiting. Changes in detail or structure may be made without departing from the spirit of the disclosure as defined in the appended claims. 
     When introducing elements of the present disclosure or the preferred embodiment(s) thereof, the articles “a”, “an”, “the”, and “said” are intended to mean that there are one or more of the elements. The terms “comprising”, “including”, and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. 
     As various changes could be made in the above constructions without departing from the scope of the disclosure, it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.