Real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure

Abstract

A system for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure includes a transdermal infrared spectrophotometric sensor which can be connected to a patient for collecting biomarker data which is outputted to a cloud based platform and analyzed in real time for determination of biomarker levels and trends of the patient in real time. A method for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure includes reporting biomarker levels and trends of the patient in real time and generating alerts to medical providers when biomarker levels or biomarker trends are abnormal. The system and method includes biomarker monitoring during post-procedure care and remote monitoring of patient biomarker levels post-discharge.

Description

REAL TIME CONTINUOUS CARDIAC INJURY BIOMARKER MONITORINGFOR PATIENTS UNDERGOING CARDIAC PROCEDURECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 595,282, filed November 01, 2023, which is hereby incorporated by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure pertains to a system and method for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedures.BACKGROUND

[0003] Procedural myocardial injury is a known challenge in patients undergoing Percutaneous coronary intervention (PCI). See Silvain J, Zeitouni M, Paradies V, Zheng HL, Ndrepepa G, Cavallini C, Feldman DN, Sharma SK, Mehilli J, Gili S, Barbato E, Tarantini G, Ooi SY, von Birgelen C, Jaffe AS, Thygesen K, Montalescot G, Bulluck H, Hausenloy DJ. Procedural myocardial injury, infarction and mortality in patients undergoing elective PCI: a pooled analysis of patient-level data. Eur Heart J. 2021 Jan 21 ;42(4):323-334. doi: 10.1093 / eurheartj / ehaa885. Erratum in: Eur Heart J. 2021 Apr 7;42(14): 1443. PMID: 33257958; PMCID: PMC7850039. These injuries could lead to periprocedural myocardial infarctions (PMI) that are known to occur frequently after elective PCI, and recent studies have suggested that the occurrence of periprocedural myocardial infarction (MI) results in increased risk for future adverse cardiac events and mortality.

[0004] PMIs manifest with an increase of biomarkers of myocardial necrosis, as observed frequently after percutaneous coronary interventions (PCI) even when the PCI procedure seems angiographically successful and otherwise uncomplicated. See Zimarino M, Affinito V. The prognosis of periprocedural myocardial infarction after percutaneous coronary interventions. Cardiovasc Revasc Med. 2013 Jan- Feb;14(l):32-6. doi: 10.1016 / j.carrev.2012.10.006. Epub 2012 Nov 17. PMID: 23164601. The scientific and clinical community including the American College of Cardiology have recently set guidelines to monitor for PMI based on electrocardiograms, and cardiac injury biomarkers such as cardiac troponin 1 / (cTnl) and creatine kinase MB (CK-MB). See Mair J, Jaffe A, Lindahl B, Mills N, Mockel M, Cullen L, Giannitsis E, Hammarsten O, Huber K, Krychtiuk K, Mueller C, Thygesen K. The clinical approach to diagnosing peri-procedural myocardial infarction after percutaneous coronary interventions according to the fourth universal definition of myocardial infarction - from the study group on biomarkers of the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC). Biomarkers. 2022 Jul;27(5):407-417. doi: 10.1080 / 1354750X.2022.2055792. Epub 2022 May 26. PMID: 35603440;PMCID: PMC9344934. See also https: / / www.acc.org / latest-in-cardiology / articles / 2014 / 07 / 18 / 14 / 54 / how- should-we-diagnose-mi-after-pci .

[0005] In Chronic Coronary Syndrome (CCS) patients with normal baseline levels of myonecrosis biomarkers like cardiac Troponin (cTn), the post-PCI cTn elevation of >3 x baseline levels, or >5 * 99th percentile URL used to define Type 4a MI, are shown to be associated with one-year mortality. Suchbiomarker levels based assessment could be used to detect ‘major’ procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischemia.

[0006] The research conducted in understanding procedural myocardial injuries have mostly considered patients with normal baseline levels of cardiac troponin. Further understanding of procedural myocardial injury in patients with varying levels of cardiac injury biomarkers may provide greater insights to the clinical and scientific community in better management of patients. These could involve stable chronic angina patients with elevated baseline levels of cardiac injury biomarkers scheduled for diagnostic catheterization procedures, as well as acute coronary syndrome patients with rapidly increasing or decreasing levels of cardiac injury biomarkers being evaluated for immediate revascularization.

[0007] There is an absence of technology available to clinicians in monitoring for real time cardiac injury in patients undergoing invasive cardiac procedures such as diagnostic catheterization electives, percutaneous interventions, coronary artery bypass graft, and cardiac transplant surgery. There remains a need for real-time cardiac injury monitoring which can provide instantaneous feedback to the surgeon and have prognostic significance of procedural myocardial injury with major adverse cardiovascular events (MACE) or long-term mortality.SUMMARY

[0008] Patients with periprocedural myocardial damage should be treated as a higher-risk cohort, carefully monitored and receive an intensified secondary prevention program. A system and method for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedures is provided herein. Monitoring and assessment of biomarker trends during a cardiac procedure and postprocedure using the system and methods described herein provide real-time visibility to procedure related insults within the coronary vasculature, including but not limited to stent thrombosis and aspirated thrombus. Despite seemingly successful procedures, patients often experience increased levels of cardiac injury biomarkers like cTnl and CK-MB. The real-time monitoring system and methods described herein include the use of a transdermal infrared spectrophotometric sensor (transdermal-ISS) to continuously detect composite acute cardiac injury biomarkers, in use cases such as real time monitoring during cardiac procedures, the transdermal-ISS (T-ISS) being configured as a wearable, non-invasive device. The transdermal-ISS can be configured as described in Applicant’s patent application WO2023064274A1 published April 20, 2023, Applicant’s patent application WO2023081449A1 published May 11, 2023, Applicant’s patent application US20220079473A1 published March 17, 2022 and Applicant’s patent application US 2020 / 0118679A1 published April 16, 2020 and issued as US Patent No. 11,257,591B2 on February 22, 2022. This monitoring and assessment of biomarker trends using the transdermal-ISS can guide optimal patient care with medical management in transient ischemic events while recommending immediate invasive assessment in the catheterization lab in suspected Acute Coronary Syndrome (ACS) patients, and / or alerting patients post-operatively to the need to seek medical consultation based on the assessed biomarker trend. As such, an advantage of the system and methods disclosed herein for the monitoring of biomarkers using a T-ISS is early intervention, which can save the myocardium of the patient from unnecessary prolonged damage, and thereby improve outcomes in patients.

[0009] The concepts described herein generally relate to systems, devices, and methods for real timecontinuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure. A patient can also be referred to herein as a subject.

[0010] An aspect of the disclosure may include a method for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure. The method includes applying a transdermal infrared spectrophotometric sensor (T-ISS) to a subject; detecting a baseline biomarker signal from the subject using the T-ISS; and determining, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal. The method can further include detecting, in real time, a real time biomarker signal from the subject using the T-ISS; and determining, using the real time biomarker signal, a real time biomarker value of the cardiac injury biomarker defined by the real time biomarker signal. The method can further include determining, using the real time biomarker signal, a real time biomarker trend of the cardiac injury biomarker defined by the real time biomarker signal.

[0011] The method can further include determining, using at least one of the real time biomarker value and the real time biomarker trend, a susceptibility of the subject toward periprocedural myocardial infraction (PMI) in real time during performance of a percutaneous coronary intervention (PCI) of the subject. The method can further include assessing, in real time, the real time biomarker trend for abnormality; and outputting an alert when the assessed biomarker trend is determined to be abnormal; wherein assessing the biomarker trend for abnormality includes comparing the assessed biomarker trend to the baseline biomarker value. An aspect of the disclosure may include wherein the alert includes an indicator of one or more of myocardial infarction (MI), a transient ischemic event, a myocardial infarction (MI) event, or a major adverse cardiovascular event (MACE), of the subject.

[0012] Another aspect of the disclosure may include a system for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure. The system includes a transdermal infrared spectrophotometric sensor (T-ISS) applied to a subject; wherein the T-ISS is configured to detect a baseline biomarker signal from the subject; the system configured to determine, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal.

[0013] An aspect of the disclosure may include a method for monitoring cardiac injury of a subject, the method comprising: prior to performing a cardiac procedure on a subject: applying a transdermal infrared spectrophotometric sensor (T-ISS) to the subject; detecting a baseline biomarker signal from the subject using the T-ISS; and determining, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal. The method can further include performing the cardiac procedure on the subject; during performing of the cardiac procedure: detecting in real time, a real time biomarker signal from the subject using the T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; and determining in real time, using the real time biomarker signal, a real time biomarker trend.

[0014] The method can further include outputting to a display, in real time, the biomarker baseline value, the real time biomarker value, and the real time biomarker trend. The method can further include determining, using the real time biomarker trend, a susceptibility of the subject toward periprocedural myocardial infraction (PMI) in real time during performing of cardiac procedure.

[0015] The method can further include, during post-procedure observation: detecting in real time, a real time biomarker signal from the subject using the T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; determining in real time, using the real time biomarker signal, a real time biomarker trend; and comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal. The method can further include, in response to the alert, at least one of: assessing a cardiac condition of the subject; medically managing the subject for transient ischemia; or performing an invasive cardiac assessment of the subject.

[0016] The method can further include discharging the subject from post-procedure observation; applying an ambulatory T-ISS to the subject; detecting in real time, a real time biomarker signal from the subject using the ambulatory T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; determining in real time, using the real time biomarker signal, a real time biomarker trend; comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal; and outputting an alert when the assessed biomarker trend is determined to be abnormal. The method can further include wherein the alert is at least one of: an alert to the subject to obtain medical assistance; an alert to a care provider to assess a cardiac condition of the subject; or an alert to a first responder to provide medical assistance to the subject. In one aspect of the disclosure, the alert is outputted via the ambulatory T-ISS.

[0017] The above features and advantages, and other features and advantages, of the present teachings are readily apparent from the following detailed description of some of the best modes and other embodiments for carrying out the present teachings, as defined in the appended claims, when taken in connection with the accompanying drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] FIG. 1 A schematically illustrates a system for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure, the system including a transdermal infrared spectrophotometric sensor (T-ISS) and cloud based platform in communication with the T-ISS.

[0019] FIG. IB schematically illustrates the system of FIG. 1A, further adapted for real time continuous cardiac injury biomarker monitoring for patients post-cardiac procedure.

[0020] FIG. 2A schematically shows a transdermal infrared spectrophotometric sensor (T-ISS).

[0021] FIG. 2B is a schematic illustration of another embodiment of the T-ISS for remote patient monitoring for extended periods of observation post-procedure.

[0022] FIG. 3 schematically illustrates a method for monitoring biomarker levels and biomarker trends of a patient during a cardiac procedure, during a post-procedure period, and during a post-discharge period, the method utilizing the system of FIGS. 1A and IB and the transdermal-ISS of FIGS. 2A and 2B.

[0023] FIG. 3 A is a sectioned view of FIG. 3, showing sections 3-1, 3-2, 3-3, 3-4 and 3-5.

[0024] FIG. 3-1 is an enlarged view of section 3-1 of FIG. 3 A.

[0025] FIG. 3-2 is an enlarged view of section 3-2 of FIG. 3 A.

[0026] FIG. 3-3 is an enlarged view of section 3-3 of FIG. 3 A.

[0027] FIG. 3-4 is an enlarged view of section 3-4 of FIG. 3 A.

[0028] FIG. 3-5 is an enlarged view of section 3-5 of FIG. 3 A.

[0029] FIG. 4 schematically illustrates correlation between the signal output of the transdermal-ISS of FIGS. 2A and 2B and acute cardiac injury biomarkers in a pre-clinical model that induces myocardial ischemia, infarction and passive perfusion in a porcine subject.

[0030] FIG. 4-1 is an enlarged view of section 4-1 of FIG. 4.

[0031] FIG. 4-2 is an enlarged view of section 4-2 of FIG. 4.

[0032] FIG. 4-3 is an enlarged view of section 4-3 of FIG. 4.

[0033] FIG. 4-4 is an enlarged view of section 4-4 of FIG. 4.

[0034] FIG. 5 schematically illustrates correlation between the signal output of the transdermal-ISS of FIGS. 2A and 2B and a patient condition during a cardiac procedure, in a first patient case example.

[0035] FIG. 6 schematically illustrates correlation between the signal output of the transdermal-ISS of FIGS. 2A and 2B and a patient condition during a cardiac procedure, in a second patient case example.

[0036] FIG. 7 schematically illustrates correlation between the signal output of the transdermal-ISS of FIGS. 2A and 2B and a patient condition during a cardiac procedure, in a third patient case example.

[0037] FIG. 8 schematically illustrates system 100 of FIG. 1, including the T-ISS of FIG. 2B adapted to monitor biomarkers of chronic diseases including diabetes, kidney disease and heart failure.

[0038] FIG. 8A schematically illustrated biomarker data collected via the T-ISS of FIG. 8 for an example biomarker.

[0039] FIG. 8A schematically illustrated biomarker data collected via the T-ISS of FIG. 8 for another example biomarker.

[0040] FIG. 8A schematically illustrated biomarker data collected via the T-ISS of FIG. 8 for yet another example biomarker.

[0041] FIG. 8A schematically illustrated biomarker data collected via the T-ISS of FIG. 8 for yet another example biomarker.DETAILED DESCRIPTION

[0042] Monitoring and assessment of biomarker trends of a patient (subject) during a cardiac procedure and post-procedure using the system and methods described herein provide real-time visibility to procedure related insults within the coronary vasculature, including but not limited to stent thrombosis and aspirated thrombus. Despite seemingly successful procedures, patients often experience increased levels of cardiac injury biomarkers like cTnl and CK-MB. A system 100 for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure, which may also be referred to as a real time biomarker monitoring system 100 or biomarker monitoring system 100, is provided herein. Additionally, a method 300 for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure using the biomarker monitoring system 100 is provided herein, which may also be referred to as a real time biomarker monitoring method 300 or biomarker monitoring method 300, as described in specification and included schematic representations, and as illustrated by the attached figures. The real-time monitoring system 100 and method 300 described herein include the use of a transdermal infrared spectrophotometric sensor (transdermal-ISS) 10 to continuously detect composite acute cardiac injury biomarkers, in use cases such as real time monitoring during cardiac procedures, the transdermal-ISS (T-ISS) 10 being configured as a wearable, non-invasive device, which may be a wireddevice such as the T-ISS 200 shown in FIG. 2A, or a portable, wireless device 600 shown in FIG. 2B. As referred to herein, the T-ISS device 10 generally refers to the wired T-ISS 200 and the wireless T-ISS 600, unless specified otherwise and / or as required by use conditions. The transdermal-ISS 10 can be configured as described in Applicant’s patent application WO2023064274A1 published April 20, 2023, Applicant’s patent application WO2023081449A1 published May 11, 2023, Applicant’s patent application US20220079473A1 published March 17, 2022 and Applicant’s patent application US 2020 / 0118679A1 published April 16, 2020 and issued as US Patent No. 11,257, 591 B2 on February 22, 2022. Monitoring and assessment of biomarker trends using the transdermal-ISS 10 can guide optimal patient care with medical management in transient ischemic events while recommending immediate invasive assessment in the catheterization lab in suspected Acute Coronary Syndrome (ACS) patients, and / or alerting patients post-operatively to the need to seek medical consultation based on the assessed biomarker trend. As such, an advantage of the system 100 and method 300 disclosed herein for the monitoring of biomarkers using a T-ISS 10 is early intervention, which can save the myocardium of the patient from unnecessary prolonged damage, and thereby improve outcomes in patients.

[0043] In the drawings, like reference numbers represent like or similar components throughout the several figures, wherever possible, and the elements shown in the figures are not necessarily to scale or proportion. Accordingly, the particular dimensions and applications provided in the drawings presented herein are not to be considered limiting. Reference numbers may not be presented in order. As used in this specification, the term “or” includes any one, and all, combinations of the associated listed items. The term “any of’ is understood to include any possible combination of referenced items, including “any one of’ the referenced items.

[0044] Referring to FIGS. 1A and IB, the system 100 and method 300 for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure is shown. A patient may also be referred to herein as a subject. One aspect of the system 100 is shown in FIG. 1A as a system 100a for real time continuous cardiac injury biomarker monitoring for a patient undergoing a cardiac procedure at a catheterization lab 30, and includes a transdermal-ISS 10, shown in the illustrative example as a wired T-ISS 10, 200 and in further detail in FIG. 2A. The catheterization lab 30 may be, for example, located in a larger care facility such as a surgical center or hospital equipped for performing cardiac procedures including but not limited to percutaneous coronary intervention (PCI). The term “catheterization lab” is not intended to be limited and it would be understood that facility 30 may be any facility equipped to perform cardiac procedures on a patient.

[0045] Referring to FIG. 2A and as described in Applicant’s patent application WO2023064274A1, the transdermal ISS 200 includes a main body 202, cover 204, and a base 206. The main body 202 houses electrical and optical components therein, including an internal reflection element (IRE). The cover 204 is configured to removably cover a portion of the main body 202. The base 206, in this embodiment, is configured to enable charging of electrical components of the main body 202 and may be plugged into a power source, and / or may be configured to provide wireless charging to electrical components within the main body 202. In this configuration, the base 206 also includes an optional indicator light 210 which may be provided to indicate a charging state or other operational state of the electronics of the main body 202 and / or of the transdermal optical sensing system 200. The main body 202, in this illustrative embodiment,includes an operational button 212 configured to enable powering the electronics of the main body 202 on and off. Further, in some embodiments, the operational button 212 may be configured to enable use of the transdermal ISS 200. In some embodiments, the operational button 212 may be omitted, and the transdermal infrared spectrophotometric sensor 200 may be configured to be controlled or operated by a remote device (e.g., remote controller, mobile device, computer, smart phone, etc.). The transdermal-ISS 200 includes an internal reflection element (IRE) and a retention member for retaining the T-ISS 10, 200 to the patient in use. During use, for example, when monitoring biomarkers of a patient during a cardiac procedure, the exposed portion of the IRE is arranged as described in Applicant’s patent application WO2023064274A1, such that the wrist or other part of a patient’s body may be arranged in contact with the IRE. The main body 202 may be shaped and contoured to aid in ensuring that appropriate contact between the epidermis of a patient remains in contact with the IRE when performing a monitoring operation. The retention member may be a strap, band or other structure that can partially wrap about a patient’s wrist and retain the wrist in a position of constant contact with the IRE of the T-ISS 10, 200. The transdermal infrared spectrophotometric sensor 200 may be a portable or semi-portable device. In some embodiments, the transdermal infrared spectrophotometric sensor (T-ISS) 200 may be configured and sized for bedside use, and thus has a relatively small form factor that can fit on a hospital bed, or the like, with a patient and not disrupt such patient.

[0046] One aspect of the system 100 is shown in FIG. IB as a system 100b for real time continuous cardiac injury biomarker monitoring for a patient post-operatively, e.g., after undergoing a cardiac procedure and / or after being discharged from the operating facility and includes a transdermal-ISS 10, shown in the illustrative example as a wireless T-ISS 10, 600 and in further detail in FIG. 2B. Referring to FIG. 2B and as described in Applicant’s patent application WO2023064274A1, the transdermal ISS 600 includes two main body portions 602a, 602b that are configured to house power and control features of the transdermal infrared spectrophotometric sensor 600 (e.g., controller, electrical power, etc.). A first main body portion 602a may house the optical components and a second main body portion 602b may house the processing and control components of the transdermal optical sensing system 600. In this configuration, the T-ISS 600 is arranged as a watch-type device or wrist-wearable and may be worn by a patient. As such, the T-ISS 600 includes two retention members 604 that form a wristband or similar structure. The transdermal optical sensing system 600 includes an IRE 606 on the first main body portion 602a for contact with the skin of a patient that wears the transdermal optical sensing system 600. An operational button 608 may be provided to perform measurements on demand and / or for powering the transdermal optical sensing system 600 on and off.

[0047] As demonstrated in method 300 shown in FIGS. 3, 3A and 3-1 through 3-5, during an elective cardiac catheterization procedure conducted, in the illustrative example, at a catheterization lab 30, the T- ISS 10 is administered on the patient’s volar surface of the wrist during pre-procedure preparation (see step 325 of method 300 in FIG. 3-1). Biomarker data collected during pre-procedure preparation establishes a baseline for the transdermally derived composite cardiac injury biomarkers prior to performance of the catheterization procedures on the patient. Once vitals (step 320 of method 300) and continuous trending biomarker baselines are established, the cardiac catheterization procedure is initiated on the patient (step 330 of method 300).

[0048] Referring to FIGS. 1A and IB, real-time signals of the composite cardiac injury biomarkers associated with underlying pathophysiology in the coronary vessels are transdermally acquired by the T- ISS 10 and transmitted to a cloud based platform 20 wirelessly, e.g., via cellular network or WiFi connection. The continuous streaming signals can also be transmitted via Bluetooth™ to an edge connected device available in the catheterization lab 30. Signal processing and trend analysis are computed in real-time within the cloud platform 20, which outputs, via the internet, a streaming signal output and biomarker trend analysis to the catheterization lab 30, such that the biomarker trend analysis is then available for instantaneous visual feedback on a monitor / display in the catheterization lab 30. The cloud based platform 20 can include one or more processors that can execute one or more computer executable instructions, including instructions for receiving and analyzing the real-time signals of the composite cardiac injury biomarkers received from the T-ISS 10, to determine biomarker trends in real time. The cloud based platform 20 can further include a memory, which is a volatile and / or non-volatile memory to store the computer executable instructions in addition to data items such as databases, data structures, files and other electronic data that facilitates the operation of the method 300. The analysis of the biomarker signals can be performed by the cloud based platform 20, for example, using a prediction model, machine learning and / or artificial intelligence. The cloud based platform 20 can include one or more algorithms for the processing of the biomarker signals in real time, and for determining and outputting biomarker trends to the catheterization lab 30. The cloud based platform 20 can be configured to compare, in real time, the biomarker trend to a baseline biomarker value, a reference trend, and / or a threshold biomarker value, and where an abnormal biomarker trend or value is detected, for example, in comparison to the baseline biomarker value, reference trend or threshold biomarker value, the cloud based platform 20 can output an alert in real time to one or more of the medical provider, a care provider, an emergency responder 40, and / or the patient, indicating an abnormal biomarker trend or value has been detected. The alert can include, for example, a prognostic indicator of an MI or MACE event, an indicator to modify the cardiac procedure being conducted, or, if outputted post-operatively, an indicator to provide or seek medical evaluation or treatment.In another aspect FIG. IB shows the system 100, 100b configured for post-operative remote monitoring of biomarker trends, for example, after the patient has been discharged from the catheterization lab 20. System 100b further includes an emergency responder 40 configured such that the emergency responder 40 may receive alerts directly from the T-ISS 20, 600 monitoring the post-operative patient, such that the emergency responder 40 can initiate an emergency response at the earliest possible detection of an abnormal biomarker value or abnormal biomarker trend, to minimize cardiac damage to the patient.

[0049] The system 100 may further include, as indicated by method 300, additional standardized sensors for monitoring cardiac patients undergoing cardiac procedures, including, for example, sensors for monitoring blood pressure, blood oxygen saturation levels, heart rate, respiration, pulse, temperature, etc, as would be known to one skilled in the art.

[0050] The system 100 and method 300 is advantaged by being configured to provide biomarker trends in real time, where real-time status of the coronary circulation plays a role in determining susceptibility toward periprocedural myocardial infarction (PMI) at the time of percutaneous coronary intervention (PCI). Susceptibility toward PMI at the time of PCI can be closely monitored using the system100 by continuously trending the levels of cardiac injury biomarkers of interest, as detected by the T-ISS 10. These biomarkers could be biomarkers of myocardial ischemia (h-FABP3, fragments of cardiac Troponin, suPar) and infarction (cardiac Troponin, CK-MB) downstream from coronary occlusions, or biomarkers of inflammatory response to coronary insults from distal epithelial cells in the coronary arteries (PTX3, CRP, IL-6).

[0051] The transdermal infrared spectrophotometric sensor (T-ISS) 10, 200, 600 (see FIGS. 1A, IB, 2A, 2B) is designed to acquire infrared signals through the skin which are associated with a composite of acute cardiac injury biomarkers. The T-ISS 10 demonstrates, in illustrative examples as shown in FIGS. 4, 5, 6 and 7, continuous monitoring for identifying cardiac injury in real time during performance of a cardiac procedure, and to evaluate safety endpoints in post procedure monitoring for PMIs. The identification of cardiac injury in real time with a transdermal-ISS 10 on patients through a procedure avails instantaneous feedback to the surgeon and posits the opportunity in either continuing, modulating or retracting the interventional procedure in the best interest of the patient.

[0052] As demonstrated by the illustrative examples shown in FIGS. 4, 5, 6 and 7, a change in baseline trends of a transdermally derived composite of cardiac injury biomarkers represents an underlying pathophysiological transition in the coronary arteries and associated myocardium. An absolute change from a baseline, such as a “spike” beyond a certain predefined threshold for absolute infrared absorption of the composite cardiac injury biomarkers, signifies a transient ischemic event induced insufficiency in the coronary circulation. Similarly, a relative change from a baseline, such as an “acute rise or fall” represented by pre-defined standard deviations from the mean of the baseline within a predefined time interval, signifies acute coronary insufficiency.

[0053] Acute coronary burden leads to physiological changes in the epithelial cells lining the coronary vessels, around the area of coronary insult. This physiological transition is observed by the change in infrared absorption signals acquired through the skin by the T-ISS 10. Referring to FIG. 4, enlarged in FIGS. 4-1, 4-2, 4-3 and 4-4, shown is an example of the release kinetics associated with composite cardiac injury biomarkers (inflammatory, ischemic and infarction biomarkers such as PTX3, heart type fatty acid binding protein(h-FABP), Troponin, Tropomyosin, Troponin C etc.) is demonstrated in a pre-clinical model of induced ischemia, infarction and passive perfusion illustrated in FIGS. 4, 4-1, 4- 2, 4-3 and 4-4. The 90 minute balloon inflation induced coronary occlusion in the left anterior descending artery of the porcine subject of the pre-clinical model leads to a cascade of physiological changes due to immediate cessation of blood supply. The composite biomarker infrared absorption signal trends are associated with mass spectrometric analysis of serial blood samples collected at various points (prior to balloon inflation, during balloon inflation and post balloon deflation). As observed in FIGS. 4-1 and 4-2, the T-ISS baselines (samples 0, 1, 2, 3) are relatively stable, and begin to rise shortly after balloon inflation (samples 4, 5, 6) and continue to rise post deflation, shile the blook-based measurements for cardiac Troponin I rise only after balloon deflation (samples 7, 8, 9, 10, 11, 12). As also observed via exosome based profiling, extraction and analysis in FIG. 4-3, levels of PTX3 rise commensurate with T-ISS signals. Exosomes further reveal the presence of Troponin I, Tropomyosin, Troponin C ( (FIG. 4-4). The correlative approach to mass spectrometry-based proteomics enables the discovery of biomarkers, and the cascade of release and clearance kinetics associated with physiological changes induced as the bodytransitions through various acute and chronic disease states.

[0054] The trending of the transdermally derived biomarkers of a patient sensed using the T-ISS 10 during complex PCI procedures performed on the patient, as demonstrated in the pre-clinical model of induced ischemia, infarction and passive perfusion illustrated in FIGS. 4, 4-1, 4-2, 4-3 and 4-4, and as further demonstrated in the PCI case study examples shown in FIGS. 5-7, allows for a high sensitivity and specificity in real-time detection of cardiac insults of a patient though monitoring of the transdermally derived biomarkers of the patient. The demonstrated correlation that biomarker levels of a patient detected by the transdermal-ISS 10 closely track the patient’s PCI procedure-related events, with biomarker levels returning to normal (baseline) in successful patient cases, and, in contrast, rising to levels post-procedure in cases that eventually led to adverse outcomes for the patient, is foundational to optimizing real time intervention during the procedure and / or post-operatively, to optimize the success of the outcome for the patient.

[0055] It would be understood that the illustrative examples related to cardiac conditions are nonlimiting, and that monitoring the trend of the biomarkers of both chronic and acute disease states including but not limited to cardiac related states enhances the visibility into disease progression and recovery states. For example, chronic diseases such as coronary artery disease, chronic heart failure, diabetes, kidney disease, and transitioning through acute episodes such as acute coronary syndrome, acute heart failure, hypotension, and acute kidney injury respectively can be monitored using the system 100 and T-ISS 10, as shown in FIG. 8. Correlation between the absorption signal outputted by T-ISS 10 and biomarkers of acute heart failure such as nt-proBNP (FIG. 8B), biomarkers of acute kidney injury such as creatinine (FIG. 8C), and biomarkers to evaluate average blood sugar over a time period such as HbAlc (FIG. 8D) can be used in a monitoring system such as illustrated in FIGS, la and lb, using the method 300 shown in FIG. 3 adapted for other non-cardiac procedures and / or disease states. By way of illustrative examples, biomarker discovery and continuous monitoring enables effective disease phenotyping in various acute inflammatory responses such as associating with lactate and various acute phase reactants for monitoring sepsis, or biomarkers associated with cancer remission and relapse, or biomarkers in orphan diseases. Similar techniques can be employed at understanding drug-drug interactions and modulating dosage for optimal management of patients using T-ISS monitoring of relevant biomarkers as described herein.

[0056] Referring to FIGS. 3, 3A and FIGS 3-1 through 3-5, method 300 for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure using the system 100 is illustrated. For purposes of illustration, FIG. 3-1 through FIG. 3-5 showing enlarged sections 3-1 through 3-5 of FIG. 3 as referenced in FIG. 3A. The description of method 300 may move between a description of the steps of method 300 and the individual components of system 100 and figures demonstrating the method 300. Referring to FIGS. 3-1 through 3-5, an example method 300 for real time continuous cardiac injury biomarker monitoring for a patient undergoing a cardiac procedure is shown, beginning at Steps 305 and 310 where a patient is diagnosed as having an acute coronary syndrome (ACS) condition or a chronic coronary syndrome (CCS) requiring a cardiac procedure. At Step 315, the patient is scheduled for the cardiac procedure based on the diagnosis of an ACS or CCS condition, and is admitted to a catheterization lab 20 or like facility, such as a surgical center, hospital or other medical facility for the cardiac procedure.

[0057] At Step 320, the patient is prepared for the cardiac procedure, by being connected toconventional vitals monitoring equipment such as a blood pressure cuff, pulse oximeter, heart monitor, etc., to establish vitals baseline measurements, including for example, blood pressure, pulse, heart rate, and blood oxygen level. At Step 325, the patient is further prepared for the cardiac procedure, by being connected to a transdermal infrared spectrophotometric sensor (T-ISS) 10, to establish transdermal biomarker baselines using the system 100, 100a shown in FIG. 1A. At Step 325, the T-ISS 10 continuously detects composite acute cardiac injury biomarkers from the patient, and transmits the collected biomarker data to the cloud based platform 20 for real time analysis, including establishing baseline and real time trending of the monitored biomarkers.

[0058] At Step 330, the cardiac procedure, which in an illustrative example is a percutaneous coronary intervention, is initiated on the patient. At Step 335 and Step 350, which occur contemporaneously and are conducted continuously throughout the cardiac procedure, vitals monitoring using conventional vitals monitoring equipment, and real time biomarker monitoring using the T-ISS 10 in communication with cloud based platform 20 are conducted. At step 340, in the event that vitals monitoring detects an abnormal vital condition, interventions are taken as needed in the cardiac procedure to return the vitals to the vitals baseline or acceptable condition.

[0059] At step 350, the cloud based platform 20 continuously receives and analyzes the biomarker signals outputted by the T-ISS 10 and provides real time reporting and trend analysis of the patient’s biomarkers to the catheterization lab 30. At step 355, in the event that the cloud based platform 20 detects, in real time, an abnormal biomarker trend and / or a biomarker value outside acceptable thresholds or limits, the cloud based platform 20, in real time, outputs an alert indicating the abnormal biomarker condition. At Step 360, in response to the alert of an abnormal biomarker condition or trend, interventions are taken and / or adjustments in the cardiac procedure are made as needed to return the biomarker level of the patient to the biomarker baseline level and / or to a biomarker level within acceptable threshold values.

[0060] At Step 365, after completion of the cardiac procedure, the patient is monitored in a postprocedure or step down unit within the medical facility 30. The post-procedure unit can be, for example, a step down unit, a Post Anesthesia Care Unit (PACU), a Cardiac Care Unit (CCU) or the like. During postprocedure care, at Step 370 and Step 385, which occur contemporaneously and are conducted continuously throughout post-procedure care, vitals monitoring using conventional vitals monitoring equipment, and real time biomarker monitoring using the T-ISS 10 in communication with cloud based platform 20 are conducted. At step 375, in the event that vitals monitoring detects an abnormal vital condition, interventions are taken as needed in post-procedure care to return the vitals to the vitals baseline or to an acceptable condition.

[0061] At step 390, the cloud based platform 20 continuously receives and analyzes the biomarker signals outputted by the T-ISS 10 and provides real time reporting and trend analysis of the patient’s biomarkers to the post-procedure unit 30. At step 395, in the event that the cloud based platform 20 detects, in real time, an abnormal biomarker trend and / or a biomarker value outside acceptable thresholds or limits, the cloud based platform 20, in real time, outputs an alert indicating the abnormal biomarker condition to the health care provider in the post-procedure unit 30. At Step 395, in response to the alert of an abnormal biomarker condition or trend, the health care provider assesses the patient’s clinical prognosis for Acute Coronary Syndrome (ACS) at Step 400.

[0062] If suspicion for ACS is found at Step 400, the patient, at Step 405 is scheduled for Invasive Assessment of the patient’s post-procedure condition, and the patient is returned to the catheterization lab 30 for invasive assessment, following the method steps beginning at steps 320 and 325 to prepare the patient for another cardiac procedure. If suspicion for ACS is not found at Step 400, then the patient, at Step 405, is medically managed for transient ischemia, and real time monitoring of the patient’s biomarker levels and biomarker trend continues at Step 385, concurrent with monitoring of the patient’s vitals at Step 370.

[0063] At Step 420, prior to discharge of the patient from the post-procedure care unit, the patient’s biomarker trends are reviewed and, if no abnormal biomarker trends have been detected, the patient is scheduled for discharge at Step 425 and discharged at step 430. Post-discharge care is provided at Step 435, which can include conventional out-patient follow-up.

[0064] If, at Step 420, if it is determined that abnormal biomarker trends or biomarker levels were detected during the post-procedure period, continuous monitoring of the patient’s biomarkers using the T- ISS 10 may be extended for a period of time, for example, in a step-down care unit, as indicated at Step 440. At Step 445, if abnormal biomarker trends are detected during the extended monitoring period, the method returns to Step 395, with an alert to the health care provider to assess the patient’s clinical prognosis, the method then continuing from Step 395. If at Step 445, no abnormal biomarker trends are detected during the extended monitoring period, the method continues to Step 450 where the patient is evaluated for monitoring of biomarker trends for a pre-defined period of observation in a remote setting (home, nursing care facility, etc.) other than the medical care facility 30. If continued monitoring of biomarker trends is indicated, the patient is discharged at Step 455 with a T-ISS 10 unit, such as the unit 600 shown in FIG. 2a, for ambulatory monitoring. At Step 460, the patient wears the T-ISS 10, 600 during the period of continuous monitoring, during which biomarker data collected by the T-ISS 10, 600 is transmitted to the cloud based platform 20 as shown in FIG. IB for real time analysis and trend prediction.

[0065] At Step 465, in the event that the cloud based platform 20 detects, in real time, an abnormal biomarker trend and / or a biomarker value outside acceptable thresholds or limits, the cloud based platform 20, in real time, outputs an alert at Step 470 to a first responder 35 or integrated on-call healthcare provider 40, indicating the abnormal biomarker condition to the alerted first responder 35 or alerted health care provider 40. The patient may also be alerted of the abnormal biomarker trend, for example, via an alert outputted by the T-ISS 40. At Step 395, in response to the alert of an abnormal biomarker condition or trend, the first responder 35 and / or the health care provider 40 assesses the patient for suspicion for Acute Coronary Syndrome (ACS) at Step 475. If suspicion for ACS is confirmed, the patient, at Step 480 is scheduled for cardiac assessment, and if needed, is scheduled for an additional cardiac procedure according to the method 300.

[0066] If at Step 475, suspicion of ACS is not found, monitoring of the patient’s biomarker levels and biomarker trend using the T-ISS 10 continues for the duration of the ambulatory monitoring period, until discharge of the patient to outpatient follow-up at Step 435. Note that additional, or fewer, steps may be included with the method 300 shown in the figures. The system 100 created with the method 300 and the system 100 components described and illustrated herein may be utilized in various combinations as indicated by the cardiac procedure being conducted, the results of the biomarker monitoring, the patientcondition, the patient location within a medical facility, care facility, or other patient location, and the optional use of ambulatory monitoring of the patient using the T-ISS 10, 600.

[0067] Cardinal case examples illustrative of the effectiveness of method 300 and system 100 for real time continuous cardiac injury biomarker monitoring of a patient undergoing a cardiac procedure are illustrated by FIGS. 5, 6 and 7. In the example shown in FIG. 5, the patient undergoes a complex PCI for complete total occlusion in the left anterior descending artery (LAD) in tachypneic patients with elevated transdermal biomarker levels corroborated with elevated blood-based cardiac Troponin I trends. Referring to FIG. 5, at point 5 a in the procedure timeline, a baseline biomarker level is determined using data collected in real time via a T-ISS 10 connected to the patient. FIG. 5 illustrates the biomarker values obtained during the timeline of the procedure, and the resultant biomarker trend. Angiographic findings for initial thrombectomy in the LAD, followed by aspirated thrombus addressed by a follow-on thrombectomy are demonstrated in the instantaneous visualization of transdermal derived biomarkers during procedure at the various points 5b. The illustrated procedure includes angioplasty at point 5c and injection at 5d, the visualization showing the response in the biomarker trend to these actions. The cardiac procedure is completed at point 5e, at which time the biomarker monitoring and trend analysis is further extended into the PACU monitoring to ensure a return to biomarker baselines at point 5f, and safety to discharge. Biomarker levels of patients sensed using transdermal-ISS 10 in real time, during performance of the cardiac procedure, track closely with procedure related events shown at points 5a, 5b, 5c, 5d, 5e and 5f. In the illustrative example, the biomarker levels are shown returning from post-procedure levels at 5e back to normal levels at point 5f.

[0068] Another cardinal example is illustrated in FIG 6, showing a patient undergoing a complex PCI for complete total occlusion in the distal left main artery. During the procedure, a T-ISS 10 was connected to the patient and biomarker data outputted to the cloud based platform 20 of system 100, for analysis and real time visualization of the biomarker values and biomarker trends, as shown in the timeline representation of the biomarker trends in FIG. 6. At point 6a, a baseline biomarker value is established using data collected from the patient. As indicated at points 6b, revascularization was attempted retrograde via a vein graft, to meet anterograde PCI via LCX. The result was an unsuccessful revascularization over an extended time period that reached the limits of radiation, ultimately leading to a major adverse cardiovascular event of fatality. FIG. 6 illustrates the biomarker levels of the patient determined via the T-ISS 10 corresponding to additional events including defibrillation at point 6c and angioplasty at points 6d. An elevated biomarker level is sustained post procedure as shown at point 6e. The observed biomarker levels of the patient, sensed using the wearable transdermal-ISS, track closely with the procedure related events, with the biomarker levels rising post procedure (point 6e). The patient presented exacerbated symptoms post-procedure and was further evaluated in the catheterization lab 30. The patient died two days post discharge.

[0069] Referring to FIG. 7, an example of ST-elevation Myocardial Infarction, a time critical event requiring immediate revascularization, the correlation between the transdermally derived trending biomarker levels from the T-ISS 10 determined by the cloud based platform 20 is illustrated, demonstrating the prognostic relevance of monitoring cardiac biomarkers prior to procedure, for the detection of a cardiac condition in real time, such that an optimal interventional strategy can occur tomitigate cardiac damage at the earliest possible time. The real-time identification of cardiac injury, using the system 100 including a transdermal-ISS 10 and the method 300 described herein, provides immediate feedback to medical interventionists enabling them to make informed decisions during cardiac procedures. Additionally, post-procedure monitoring of composite cardiac injury biomarker levels can inform patient management of suspicion of ACS prior to discharge. As depicted in the method 300 shown in FIGS. 3, 3A and FIGS. 3-1 through 3-5, monitoring for abnormal trends, such as “spikes” and “acute rise or falls” in composite biomarkers can facilitate an immediate alert notification workflow for the cardiologist so they can proactively adjust their procedures for optimal outcome during the procedure itself. Similarly, monitoring for these abnormal trends in the post-procedure setting of a post anesthesia care unit or cardiac observation unit can enable timely attention from the attending cardiologist, and thereby schedule the patient for an earlier intervention and / or extended monitoring during hospital length of stay.

[0070] As depicted in the method 300 shown in FIGS. 3, 3A and FIGS. 3-1 through 3-5, in intermediate risk cases, such as patients where revascularization was suboptimal, or the patients experience intermittent episodes of transient ischemic events / re-infarctions, or patients have high risk factors for reinfarctions, the patients can be discharged with a T-ISS 10, 600 enabling remote patient monitoring of biomarker levels and trends, using the system 100b shown in FIG. IB. This allows integration into first responders 35 and / or on-call healthcare providers 40, who can timely respond and attend to abnormal biomarker trends seen from a remote setting. Accordingly, the patients showing abnormal biomarker trends, as detected by remote monitoring via a T-ISS 10, 600, can be accelerated to an outpatient ambulatory surgical center / in-patient cardiac catheterization laboratory in a hospital, or scheduled for telehealth / out-patient cardiology follow-up.

[0071] Real-time tracking of transdermally derived cardiac injury biomarkers may also enable interventional cardiologists in evaluating acuity of underlying coronary artery disease, particularly in silent myocardial infarctions (MI). An example is depicted in the acutely rising transdermal biomarker in a ST- elevation myocardial infarction FIG 7, that may go unnoticed and unattended for prolonged periods of heart muscle damage. An earlier assessment of the acute rise or fall of biomarkers can proactively activate cardiac catheterization lab preparation in anticipation of arrival of these critical patients. The improved non-invasive monitoring tools coupled with invasive cardiac procedures described for system 100 and method 300 provides cardiologists with advantaged tools and methodologies to facilitate optimal revascularization of coronary arteries, and to enhance patient safety and outcomes.

[0072] The non-invasive continuous monitoring using transdermally derived signals, as depicted by the figures and described herein related to system 100 and method 300, enables optimal clinical management in various additional scenarios for coronary artery disease settings such as:

[0073] Silent Angina Detection: The transdermal infrared spectrophotometric sensor (transdermal- ISS) 10 may detect myocardial injury, including silent angina, in patients who may not exhibit typical symptoms. This is particularly important because some individuals, especially older adults, and those with certain health conditions, may experience "silent" heart attacks without obvious chest pain or discomfort. Continuous remote monitoring of a patient by the wearable transdermal-ISS 10 from an established personalized baseline can alert healthcare providers, in real time, to silent acute coronary syndrome and myocardial injury cases and facilitate timely intervention, reducing the risk of complications, potentiallyeven preventing silent deaths.

[0074] Prinzmetal Angina Detection: Prinzmetal angina or Variant angina is caused due to sudden spasms in otherwise normal (clear of atherosclerotic plaques) coronary arteries. Prinzmetal angina presents with similar chest pain symptoms as myocardial angina generally in middle age women. These symptoms present for fifteen minutes, and most often occur at the quietest time of the day - between midnight and early morning. In most cases, a person sees their care provider many hours after the spontaneous episode of angina, such that making the correct diagnosis may require that the coronary artery spasm be provoked. Cardiac catheterization with provocative testing often reveals "normal” coronary arteries. A hyperventilation test, where the patient is instructed to breathe deeply and rapidly for a full six minutes, while an electrocardiogram (ECG) and echocardiography is done, may provide use in patients who have frequent episodes, but does not yield insights in those whose episodes are more sporadic or infrequent. The transdermal-ISS 10 may detect variant angina by trending normal baselines and tracking for abnormal patterns in the trend such as spikes and / or crests. These can allow for accurate diagnosis and management of patients susceptible to recurrent angina episodes. If symptoms persist for longer duration, suspected acute coronary syndrome (ACS) patients can be advanced to a cardiac catheterization lab for further evaluation.

[0075] Outpatient Situations: In outpatient settings, where patients may be undergoing diagnostic tests or receiving treatment for various cardiovascular conditions, real-time cardiac injury monitoring with transdermal-ISS 10 can enhance patient safety. It allows for the immediate identification of acute coronary syndrome and myocardial injury, thereby advancing patients for earlier cardiology assessment or immediate revascularization, enabling healthcare providers to make informed decisions and adjust the care plan as needed. This can lead to better outcomes and potentially reduce the need for hospitalization.

[0076] Paramedic Situations: Paramedics and emergency medical personnel often encounter patients with suspected cardiac issues in the field. The use of transdermal-ISS 10 to determine patient biomarker levels in real time, in paramedic situations, can aid in the rapid assessment of acute coronary syndrome and myocardial injury, helping paramedics prioritize treatment and decide whether to bypass an ED visit and transport the patient to a specialized cardiac facility such as an ambulatory surgical center (ASC) for immediate revascularization. This technology can improve the accuracy of on-site diagnoses and streamline the delivery of appropriate care, potentially saving lives in critical situations.

[0077] Remote Locations: In remote or underserved areas with limited access to advanced medical facilities, the non-invasive wearable transdermal-ISS device 10 can be a valuable tool for monitoring cardiac injury. Patients in such locations may face delays in receiving specialized care and / or may not have access to medical facilities for invasive testing. Continuous monitoring of a patent using the transdermal- ISS 10 can bridge this gap by providing early detection of myocardial injury and enabling remote healthcare providers to consult with specialists or arrange timely evacuations when necessary.

[0078] Overall, the advantages of using a transdermal-ISS device 10 in conjunction with a cloud based platform 20, as described herein related to system 100 and method 300, for the continuous monitoring of a patient’s biomarker levels, extend beyond the hospital setting, offering a versatile and potentially life-saving solution for monitoring myocardial infarction in various clinical scenarios, including silent angina, outpatient care, paramedic responses, and remote locations. Advantageously, thetransdermal-ISS 10 can be used as a method of measuring biomarker levels, for assessing patient condition in real time, in a pre-procedure diagnostic situation, during a cardiac procedure, and post-procedure for patient monitoring, to improve patient outcomes, reduce complications, and enhance the quality of care across a wide range of healthcare settings and represents a paradigm shift in the care of the cardiac patient.

[0079] Post procedure monitoring for composite cardiac injury biomarker levels in PACU, using a transdermal ISS 10, can inform management and continued monitoring of patients in step down units, wards and potentially at home by using the transdermal-ISS to monitor the patient in these various locations and through these stages. Various use scenarios are illustrated in FIG. IB and method 300 for non-hospital and / or remote monitoring of the patient's condition using the transdermal-ISS wearable device.

[0080] The following Clauses provide example configurations of a method and system for real time continuous cardiac injury biomarker monitoring for patients undergoing cardiac procedure as disclosed herein.

[0081] Clause 1 : A method for monitoring cardiac injury of a subject, the method comprising: applying a transdermal infrared spectrophotometric sensor (T-ISS) to a subject; detecting a baseline biomarker signal from the subject using the T-ISS; and determining, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal.

[0082] Clause 2: The method of clause 1, further comprising: detecting, in real time, a real time biomarker signal from the subject using the T-ISS; and determining, using the real time biomarker signal, a real time biomarker value of the cardiac injury biomarker defined by the real time biomarker signal.

[0083] Clause 3: The method of clause 2, further comprising: determining, using the real time biomarker signal, a real time biomarker trend of the cardiac injury biomarker defined by the real time biomarker signal.

[0084] Clause 4: The method of clause 3, further comprising: outputting the real time biomarker value in real time to a visual display.

[0085] Clause 5: The method of clause 4, further comprising: outputting the baseline biomarker value to the visual display.

[0086] Clause 6: The method of clause 4, further comprising: outputting the biomarker trend to the visual display.

[0087] Clause 7: The method of clause 4, further comprising: outputting the baseline biomarker value to the visual display; wherein the visual display includes a display of the real time biomarker value in real time and a display of the baseline biomarker value.

[0088] Clause 8: The method of clause 3, further comprising: determining, using at least one of the real time biomarker value and the real time biomarker trend, a susceptibility of the subject toward periprocedural myocardial infraction (PMI) in real time during performance of a percutaneous coronary intervention (PCI) of the subject.

[0089] Clause 9: The method of clause 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, silent angina of the subject.

[0090] Clause 10: The method of clause 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, prinzmetal angina of the subject.

[0091] Clause 11 : The method of clause 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, Acute Coronary Syndrome (ACS) of the subject.

[0092] Clause 12: The method of clause 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, myocardial infarction (MI) of the subject.

[0093] Clause

[0094] 13. The method of clause 3, further comprising:

[0095] detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, a transient ischemic event of the subject.

[0096] Clause 14: The method of clause 2, wherein the real time biomarker signal is detected during performance of a cardiac procedure on the subject.

[0097] Clause 15: The method of clause 2, wherein the real time biomarker signal is detected after completion of a cardiac procedure on the subject.

[0098] Clause 16: The method of clause 2, wherein the real time biomarker signal is detected during ambulatory monitoring of the subject.

[0099] Clause 17: The method of clause 16, wherein ambulatory monitoring further comprises: applying a remote transdermal infrared spectrophotometric sensor (T-ISS) to a subject; wherein the remote T-ISS is configured to output the biomarker signal to a cloud based server in wireless communication with the T-ISS; and wherein the cloud based server receives and analyzes the biomarker signal from the subject in real time.

[0100] Clause 18: The method of clause 16, wherein the ambulatory monitoring of the subject occurs post-completion of a cardiac procedure on the subject.

[0101] Clause 19: The method of clause 16, wherein the ambulatory monitoring of the subject precedes performance of a cardiac procedure on the subject.

[0102] Clause 20: The method of clause 19, wherein the ambulatory monitoring of the subject indicates an immediate revascularization of the subject is indicated.

[0103] Clause 21: The method of clause 19, further comprising: detecting, during the ambulatory monitoring of the subject, an abnormal real time biomarker trend; and outputting an alert in real time with detecting the abnormal real time biomarker trend.

[0104] Clause 22: The method of clause 21, wherein the alert is at least one of: an alert to the subject to obtain medical assistance; an alert to a care provider to assess a cardiac condition of the subject; or an alert to a first responder to provide medical assistance to the subject.

[0105] Clause 23: The method of clause 21, wherein the alert is outputted via the T-ISS.

[0106] Clause 24: The method of clause 1, wherein the cardiac injury biomarker is a composite cardiac biomarker index.

[0107] Clause 25: The method of clause 1, wherein the cardiac injury biomarker is N-Terminal Pro- B-Type Natriuretic Peptide (nt-proBNP).

[0108] Clause 26: The method of clause 1, wherein the cardiac injury biomarker is PTX3.

[0109] Clause 27: The method of clause 1, wherein the cardiac injury biomarker is Troponin.

[0110] Clause 28: The method of clause 1, wherein the cardiac injury biomarker is Tropomyosin.

[0111] Clause 29: The method of clause 1, wherein the cardiac injury biomarker is Troponin C.

[0112] Clause 30: The method of clause 1, wherein the cardiac injury biomarker is h-FABP.

[0113] Clause 31 : The method of clause 1, wherein the cardiac injury biomarker is Creatine KinaseMB (CK-MB).

[0114] Clause 32: The method of clause 1, wherein the cardiac injury biomarker is soluble urokinase Plasminogen activator receptor (suPar).

[0115] Clause 33: The method of clause 1, wherein the T-ISS is a wearable, non-invasive device configured to transmit a biomarker signal wirelessly.

[0116] Clause 34: The method of clause 3, further comprising: assessing, in real time, the real time biomarker trend for abnormality; and outputting an alert when the assessed biomarker trend is determined to be abnormal.

[0117] Clause 35: The method of clause 34, wherein assessing the biomarker trend for abnormality includes comparing the assessed biomarker trend to the baseline biomarker value.

[0118] Clause 36: The method of clause 34, wherein the abnormality is characterized by an acute rise or an acute fall in the biomarker value by pre-defined standard deviations from a mean of the biomarker baseline within a predefined time interval.

[0119] Clause 37: The method of clause 36, wherein the abnormality is an indicator of acute coronary insufficiency of the subject.

[0120] Clause 38: The method of clause 34, wherein assessing the biomarker trend for abnormality includes comparing the assessed biomarker trend to a predetermined threshold value.

[0121] Clause 39: The method of clause 38, wherein the predetermined threshold value indicates Acute Coronary Syndrome (ACS) of the subject.

[0122] Clause 40: The method of clause 38, wherein the predetermined threshold value indicates myocardial infarction (MI) of the subject.

[0123] Clause 41 : The method of clause 38, wherein the predetermined threshold value indicates a transient ischemic event of the subject.

[0124] Clause 42: The method of clause 34, wherein the alert includes an indicator of a myocardial infarction (MI) event of the subject.

[0125] Clause 43: The method of clause 34, wherein the alert includes an indicator of a transient ischemic event of the subject.

[0126] Clause 44: The method of clause 34, wherein the alert includes an indicator of a major adverse cardiovascular event (MACE) of the subject.

[0127] Clause 45: The method of clause 3, wherein the biomarker trend is defined by release and clearance kinetics of a physiological change induced by a cardiac procedure performed on the subject.

[0128] Clause 46: The method of clause 45, wherein the cardiac procedure is an angioplasty.

[0129] Clause 47: A method for monitoring cardiac injury of a subject, the method comprising: prior to performing a cardiac procedure on a subject: applying a transdermal infrared spectrophotometric sensor (T-ISS) to the subject; detecting a baseline biomarker signal from the subject using the T-ISS; anddetermining, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal.

[0130] Clause 48: The method of clause 47, further comprising: performing the cardiac procedure on the subject; during performing of the cardiac procedure: detecting in real time, a real time biomarker signal from the subject using the T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; and determining in real time, using the real time biomarker signal, a real time biomarker trend.

[0131] Clause 49: The method of clause 48, further comprising: outputting to a display, in real time, the biomarker baseline value, the real time biomarker value, and the real time biomarker trend.

[0132] Clause 50: The method of clause 48, further comprising: determining, using the real time biomarker trend, a susceptibility of the subject toward periprocedural myocardial infraction (PMI) in real time during performing of cardiac procedure.

[0133] Clause 51 : The method of clause 48, further comprising: comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal.

[0134] Clause 52: The method of clause 51, further comprising: generating an alert when the biomarker trend is determined to be abnormal.

[0135] Clause 53: The method of clause 52, further comprising: continuing, modulating, or retracting the cardiac procedure in response to the alert.

[0136] Clause 54: The method of clause 48, further comprising: during post-procedure observation: detecting in real time, a real time biomarker signal from the subject using the T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; determining in real time, using the real time biomarker signal, a real time biomarker trend; and comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal.

[0137] Clause 55: The method of clause 54, further comprising, in response to the alert, at least one of: assessing a cardiac condition of the subject; medically managing the subject for transient ischemia; or performing an invasive cardiac assessment of the subject.

[0138] Clause 56: The method of clause 54, further comprising: determining, using the real time biomarker trend, a susceptibility of the subject to Acute Coronary Syndrome during post-procedure observation.

[0139] Clause 57: The method of clause 54, further comprising: discharging the subject from postprocedure observation; applying an ambulatory T-ISS to the subject; detecting in real time, a real time biomarker signal from the subject using the ambulatory T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; determining in real time, using the real time biomarker signal, a real time biomarker trend; comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal; and outputting an alert when the assessed biomarker trend is determined to be abnormal.

[0140] Clause 58: The method of clause 57, wherein the alert is at least one of: an alert to the subject to obtain medical assistance; an alert to a care provider to assess a cardiac condition of the subject; or an alert to a first responder to provide medical assistance to the subject.

[0141] Clause 59: The method of clause 58, wherein the alert is outputted via the ambulatory T-ISS.

[0142] Clause 60: A system for monitoring cardiac injury of a subject, the system configured to perform the method of clause 1.

[0143] The detailed description and the drawings or figures are supportive and descriptive of the disclosure. While some of the best modes and other embodiments for carrying out the disclosure have been described in detail, various alternative designs, configurations, and embodiments exist for practicing the appended claims, as will be recognized by those having ordinary skill in the art.

[0144] Furthermore, any embodiments shown in the drawings, or the characteristics of various embodiments mentioned in the present description, are not necessarily to be understood as embodiments independent of each other. Rather, it is possible that each of the characteristics described in one of the examples of an embodiment can be combined with one or a plurality of other desired characteristics from other embodiments, resulting in other embodiments not described in words or by reference to the drawings. Accordingly, such other embodiments fall within the framework of the scope of the appended claims.

Claims

CLAIMS1. A method for monitoring cardiac injury of a subject, the method comprising: applying a transdermal infrared spectrophotometric sensor (T-ISS) to a subject; detecting a baseline biomarker signal from the subject using the T-ISS; and determining, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal.

2. The method of claim 1, further comprising: detecting, in real time, a real time biomarker signal from the subject using the T-ISS; and determining, using the real time biomarker signal, a real time biomarker value of the cardiac injury biomarker defined by the real time biomarker signal.

3. The method of claim 2, further comprising: determining, using the real time biomarker signal, a real time biomarker trend of the cardiac injury biomarker defined by the real time biomarker signal.

4. The method of claim 3, further comprising: outputting the real time biomarker value in real time to a visual display.

5. The method of claim 4, further comprising: outputting the baseline biomarker value to the visual display.

6. The method of claim 4, further comprising: outputting the biomarker trend to the visual display.

7. The method of claim 4, further comprising: outputting the baseline biomarker value to the visual display; wherein the visual display includes a display of the real time biomarker value in real time and a display of the baseline biomarker value.

8. The method of claim 3, further comprising: determining, using at least one of the real time biomarker value and the real time biomarker trend, a susceptibility of the subject toward periprocedural myocardial infraction (PMI) in real time during performance of a percutaneous coronary intervention (PCI) of the subject.

9. The method of claim 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, silent angina of the subject.

10. The method of claim 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, prinzmetal angina of the subject.

11. The method of claim 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, Acute Coronary Syndrome (ACS) of the subject.

12. The method of claim 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, myocardial infarction (MI) of the subject.

13. The method of claim 3, further comprising: detecting, in real time, using at least one of the real time biomarker value and the real time biomarker trend, a transient ischemic event of the subject.

14. The method of claim 2, wherein the real time biomarker signal is detected during performance of a cardiac procedure on the subject.

15. The method of claim 2, wherein the real time biomarker signal is detected after completion of a cardiac procedure on the subject.

16. The method of claim 2, wherein the real time biomarker signal is detected during ambulatory monitoring of the subject.

17. The method of claim 16, wherein ambulatory monitoring further comprises: applying a remote transdermal infrared spectrophotometric sensor (T-ISS) to a subject; wherein the remote T-ISS is configured to output the biomarker signal to a cloud based server in wireless communication with the T-ISS; and wherein the cloud based server receives and analyzes the biomarker signal from the subject in real time.

18. The method of claim 16, wherein the ambulatory monitoring of the subject occurs postcompletion of a cardiac procedure on the subject.

19. The method of claim 16, wherein the ambulatory monitoring of the subject precedes performance of a cardiac procedure on the subject.

20. The method of claim 19, wherein the ambulatory monitoring of the subject indicates an immediate revascularization of the subject is indicated.

21. The method of claim 19, further comprising: detecting, during the ambulatory monitoring of the subject, an abnormal real time biomarker trend; and outputting an alert in real time with detecting the abnormal real time biomarker trend.

22. The method of claim 21, wherein the alert is at least one of: an alert to the subject to obtain medical assistance; an alert to a care provider to assess a cardiac condition of the subject; or an alert to a first responder to provide medical assistance to the subject.

23. The method of claim 21, wherein the alert is outputted via the T-ISS.

24. The method of claim 1, wherein the cardiac injury biomarker is a composite cardiac biomarker index.

25. The method of claim 1, wherein the cardiac injury biomarker is N-Terminal Pro-B-Type Natriuretic Peptide (nt-proBNP).

26. The method of claim 1, wherein the cardiac injury biomarker is PTX3.

27. The method of claim 1, wherein the cardiac injury biomarker is Troponin.

28. The method of claim 1, wherein the cardiac injury biomarker is Tropomyosin.

29. The method of claim 1, wherein the cardiac injury biomarker is Troponin C.

30. The method of claim 1, wherein the cardiac injury biomarker is h-FABP.

31. The method of claim 1, wherein the cardiac injury biomarker is Creatine Kinase MB (CK-MB).

32. The method of claim 1, wherein the cardiac injury biomarker is soluble urokinase Plasminogen activator receptor (suPar).

33. The method of claim 1, wherein the T-ISS is a wearable, non-invasive device configured to transmit a biomarker signal wirelessly.

34. The method of claim 3, further comprising: assessing, in real time, the real time biomarker trend for abnormality; andoutputting an alert when the assessed biomarker trend is determined to be abnormal.

35. The method of claim 34, wherein assessing the biomarker trend for abnormality includes comparing the assessed biomarker trend to the baseline biomarker value.

36. The method of claim 34, wherein the abnormality is characterized by an acute rise or an acute fall in the biomarker value by pre-defined standard deviations from a mean of the biomarker baseline within a predefined time interval.

37. The method of claim 36, wherein the abnormality is an indicator of acute coronary insufficiency of the subject.

38. The method of claim 34, wherein assessing the biomarker trend for abnormality includes comparing the assessed biomarker trend to a predetermined threshold value.

39. The method of claim 38, wherein the predetermined threshold value indicates Acute Coronary Syndrome (ACS) of the subject.

40. The method of claim 38, wherein the predetermined threshold value indicates myocardial infarction (MI) of the subject.

41. The method of claim 38, wherein the predetermined threshold value indicates a transient ischemic event of the subject.

42. The method of claim 34, wherein the alert includes an indicator of a myocardial infarction (MI) event of the subject.

43. The method of claim 34, wherein the alert includes an indicator of a transient ischemic event of the subject.

44. The method of claim 34, wherein the alert includes an indicator of a major adverse cardiovascular event (MACE) of the subject.

45. The method of claim 3, wherein the biomarker trend is defined by release and clearance kinetics of a physiological change induced by a cardiac procedure performed on the subject.

46. The method of claim 45, wherein the cardiac procedure is an angioplasty.

47. A method for monitoring cardiac injury of a subject, the method comprising: prior to performing a cardiac procedure on a subject:applying a transdermal infrared spectrophotometric sensor (T-ISS) to the subject; detecting a baseline biomarker signal from the subject using the T-ISS; and determining, using the baseline biomarker signal, a baseline biomarker value of a cardiac injury biomarker defined by the baseline biomarker signal.

48. The method of claim 47, further comprising: performing the cardiac procedure on the subject; during performing of the cardiac procedure: detecting in real time, a real time biomarker signal from the subject using the T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; and determining in real time, using the real time biomarker signal, a real time biomarker trend.

49. The method of claim 48, further comprising: outputting to a display, in real time, the biomarker baseline value, the real time biomarker value, and the real time biomarker trend.

50. The method of claim 48, further comprising: determining, using the real time biomarker trend, a susceptibility of the subject toward periprocedural myocardial infraction (PMI) in real time during performing of cardiac procedure.

51. The method of claim 48, further comprising: comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal.

52. The method of claim 51, further comprising: generating an alert when the biomarker trend is determined to be abnormal.

53. The method of claim 52, further comprising: continuing, modulating, or retracting the cardiac procedure in response to the alert.

54. The method of claim 48, further comprising: during post-procedure observation: detecting in real time, a real time biomarker signal from the subject using the T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; determining in real time, using the real time biomarker signal, a real time biomarker trend; and comparing the real time biomarker trend to the baseline biomarker value to determine whether thebiomarker trend is abnormal.

55. The method of claim 54, further comprising, in response to the alert, at least one of: assessing a cardiac condition of the subject; medically managing the subject for transient ischemia; or performing an invasive cardiac assessment of the subject.

56. The method of claim 54, further comprising: determining, using the real time biomarker trend, a susceptibility of the subject to Acute Coronary Syndrome during post-procedure observation.

57. The method of claim 54, further comprising: discharging the subject from post-procedure observation; applying an ambulatory T-ISS to the subject; detecting in real time, a real time biomarker signal from the subject using the ambulatory T-ISS; determining in real time, using the real time biomarker signal, a real time biomarker value; determining in real time, using the real time biomarker signal, a real time biomarker trend; comparing the real time biomarker trend to the baseline biomarker value to determine whether the biomarker trend is abnormal; and outputting an alert when the assessed biomarker trend is determined to be abnormal.

58. The method of claim 57, wherein the alert is at least one of: an alert to the subject to obtain medical assistance; an alert to a care provider to assess a cardiac condition of the subject; or an alert to a first responder to provide medical assistance to the subject.

59. The method of claim 58, wherein the alert is outputted via the ambulatory T-ISS.

60. A system for monitoring cardiac injury of a subject, the system configured to perform the method of claim 1.

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