“Non-Invasive System And Method For Detecting And Accurately Quantifying Subclinical And Clinical Systolic And Diastolic Heart Failure” in Patent Application Approval Process (USPTO 20240008837): Cooper Health System

2024 JAN 25 (NewsRx) -- By a News Reporter-Staff News Editor at Insurance Daily News -- A patent application by the inventor HIRSH, ROBERT ALAN (Merion Station, PA, US), filed on February 6, 2023, was made available online on January 11, 2024, according to news reporting originating from Washington, D.C., by NewsRx correspondents.

This patent application is assigned to Cooper Health System (Camden, New Jersey, United States).

The following quote was obtained by the news editors from the background information supplied by the inventors: “The present state of the art uses two-dimensional ultrasound imaging to measure parameters such as ejection fraction (which is not invariant with respect to Afterload or Preload) myocardial strain, and myocardial strain rate. These prior art measurements are entirely mechanical and utterly ignore the complex and interactive electrical and patho-electrophysiological character of the transduction dysfunction in systolic and diastolic heart failure. The patho-electrophysiological character of such dysfunction involves the rapid and massive movement of Calcium ions out of one cellular compartment, the sarcoplasmic reticulum, and into the cytosol, and then following a brief pause, very rapidly, movement right back into the sacroplasmic reticulum, with each heartbeat. Present methods ignore the ion trans-membrane flux features of the disease, and only quantify the mechanical features of the disease. Membrane Flux of Ions is to a great extent represented by the reciprocal of (E-M), that is 1/(E-M), in sec{circumflex over ( )}-1. The quantity 1/(E-M), in both Systole and Diastole is essentially a membrane calcium ion flux transduction speed or rate in Systole, in ‘transductions per second’, and a ‘de-transduction rate’ in Diastole. And so present measures are effectively blind to half the physiologic features of Heart Failure, either Systolic or Diastolic, a significant defect.

“As such, the present methods of diagnosis and quantification only serve to characterize and quantify symptoms in people who are already stricken with the illness, and who are living with symptoms. These methods are not sensitive or reliable enough to serve as a screening test for people who have subclinical or preclinical disease, screening for which is not now done. If a test for ‘Pre-HF’-analagous to the use of HbA1c detect ‘Pre-Diabetes’-were feasible, it may reveal opportunities to intervene earlier in the natural history of HF with drugs such as afterload reducers, with decreasing salt intake, and with fluid management in a way that may prolong life, improve the quality of life, and modify the natural history of the disease. The feasibility of such a test would also serve to save the healthcare system a great deal of money otherwise spent on frequent re-hospitalizations for acute decompensation of HF, requiring expensive ICU stays with endotracheal intubation and mechanical ventilation. Even in patients with known clinical HF, a metric that combines electrical with mechanical character over a full range of possible contractile states would be more accurate, and reproducible, and physiologically meaningful.”

In addition to the background information obtained for this patent application, NewsRx journalists also obtained the inventor’s summary information for this patent application: “As stated above, an aim of the instant invention is the non-invasive detection and quantification of systolic and diastolic heart failure, including subclinical, not-yet symptomatic systolic and diastolic heart failure. The instant invention is a new way to process and derive clinical meaning and prognoses from physiomic data. The invention is predicated upon extracting data that is shown graphically in the Wiggers Diagram which shows the entire cardiac cycle with simultaneous data streams, the ECG, phonocardiogram, and Left Ventricular Pressure.

“The Wiggers Diagram shows the relation between the Q-wave, which is where the second derivative of the ECG in systole is maximum, and the S1heart sound, which is slightly delayed in time. This time interval is (E-M)ino, or the Intropic Electrical Mechanical Interval. Taking the point in the T-wave at which it first manifests maximal upward acceleration, and then noting the time delay to the S2 heart sound, identifies (E-M)lusi, or the Lusitropic Electrical-Mechanical Interval. When a Seismocardiogram, obtained with a precordial accelerometer, is available, then either the seismo signal that corresponds to S1 and S2, or its peak derivative values can serve as ‘M’ in the Systolic or Diastolic Electrical Mechanical Interval, (E-M) respectively. The ratio 1/(E-M) can be understood as a speed of electromechanical transduction, either inotropic or lusitropic. It has been shown that the speed of electromechanical transduction in cardiac systole (or de-transduction in cardiac diastole) is linearly proportional to the natural log of the magnitude of the strain rate, either systolic or diastolic, obtained from a 2D transthoracic echo machine, in systole, or diastole, respectively, as was described in the inventor’s earlier patent applications that are identified herein.

“Experimental results obtained by the inventor from dobutamine stress tests with a new metric of inotropic and lusitropic function, the Electrical Mechanical Intervals (E-M)ino and (E-M)lusi, have yielded two sets of linear individual calibration curves relating ln(strain rates) to 1/(E-M). Five evaluable subjects were studied. One set of five Calibration Curves describes systolic function for each of the five subjects, and the other set of five curves describe diastolic function, both for the same five individual subjects. The calibration curves are of the form ln(Strain Rate)=a+b/(E-M) where ‘a’ and ‘b’, the y-intercept and the slope, are constants for a given individual. (E-M)ino is used for the Systolic case, and (E-M)lusi is used for the Diastolic case. For both the Systolic and the Diastolic cases, plotting the y-intercept ‘a’ as a function of the slope ‘b’ for all five subjects results in a downward sloping line of intercept ‘p’ and slope ‘q’, with a very high correlation coefficient, called an “Intercept-Slope Tradeoff Function.” There is one ‘Intercept-Slope Tradeoff Function’ for the systolic case, and another for the diastolic case, the only difference being the values of the intercept ‘p’ and the slope ‘q’ .”

The claims supplied by the inventors are:

“1. A system for non-invasive detection and quantification of systolic and diastolic heart failure of a patient comprising: a non-invasive electronic heart function measurement device providing electronic outputs related to lusitropic and inotropic electrical cardiac activity; a non-invasive mechanical heart function measurement device providing mechanical outputs related to lusitropic and inotropic mechanical cardiac activity; a converting unit connected to said mechanical heart function measurement device for converting said mechanical outputs of said device into an electronic output related to said mechanical cardiac activity; a computer platform comprising a processing unit, an application program, memory means, and output means, said memory means storing a universal intercept-slope tradeoff function for inotropic function based on heart function of healthy patients and storing a universal intercept-slope tradeoff function for lusitropic function based on heart function of healthy patients; a connection from the output of said electronic heart function measurement device to the input of said processing unit; a connection from the output of said converting unit to the input of said processing unit, whereby said application program digitizes and processes said inputs to said processing unit in order to determine: (a) an inotropic electrical mechanical time interval for said patient’s heart function and a lusitropic electrical mechanical time interval for said patient’s heart function; and (b) an inotropic calibration curve of defined slope and intercept for said patient’s heart function and a lusitropic calibration curve of defined slope and intercept for said patient’s heart function; said application program comparing said inotropic calibration curve to said stored universal intercept-slope tradeoff function for inotropic function and said lusitropic calibration curve to said stored universal intercept-slope tradeoff function for lusitropic function in order make an assessment of myocardial well-being or myocardial pathology of said patient.

“2. The system of claim 1 in which said assessment is detection and quantification of systolic heart failure.

“3. The system of claim 2 in which said patient is not symptomatic.

“4. The system of claim 1 in which said assessment is detection and quantification of diastolic heart failure.

“5. The system of claim 4 in which said patient is not symptomatic.

“6. A method for non-invasive detection and quantification of systolic and diastolic heart failure of a patient comprised of the steps of placing on the chest of a patient a non-invasive electronic heart function measurement device that provides a first electronic signal related to said patient’s electrical cardiac activity including QRS complexes; connecting said first electronic signal of such electronic heart measurement device to one input of a processing system having a memory; storing in said memory of said processing system a universal intercept-slope tradeoff function for inotropic function based on heart function of healthy patients and a universal intercept-slope tradeoff function for lusitropic function based on heart function of healthy patients; digitizing within said processing system said first electronic signal; placing on the chest of said patient a non-invasive mechanical heart function measurement device that provides an output related to mechanical cardiac activity; converting said output of said mechanical heart function measurement device into a second electronic signal; connecting said converted second electronic signal to a second input of said processing system; digitizing within said processing system said second electronic signal; processing said digitized inputs to said processing system in order to determine an inotropic electrical mechanical time interval for said patient’s heart; processing said digitized inputs to said processing system in order to determine a lusitropic electrical mechanical time interval for said patient’s heart; using said inotropic interval and simultaneous inotropic myocardial strain rate data obtained from a non-invasive electronic heart function measurement device to determine an inotropic calibration curve of defined intercept and slope at rest and over varying degrees of exercise for said patient’s heart; using said lusitropic interval and simultaneous lusitropic myocardial strain rate data obtained from a non-invasive electronic heart function measurement device to determine a lusitropic calibration curve of defined intercept and slope at rest and over varying degrees of exercise for said patient’s heart; comparing said intercept and slope of said inotropic calibration curve to said stored universal intercept-slope tradeoff function for inotropic function; comparing said intercept and slope of said lusitropic calibration curve to said stored universal intercept-slope tradeoff function for lusitropic function; making an assessment of myocardial well-being or myocardial pathology of said patient using the results of said comparing of inotropic functions and said comparing of lusitropic functions.

“7. The method of claim 6 in which said assessment is detection and quantification of systolic heart failure.

“8. The method of claim 7 in which said patient is not symptomatic.

“9. The method of claim 6 in which said assessment is detection and quantification of diastolic heart failure.

“10. The method of claim 9 in which said patient is not symptomatic.

“11. A method for determining a universal intercept-slope tradeoff function for inotropic function comprising the steps of: selecting a number of heart healthy patients of diverse height, weight, age, and gender; measuring for each said healthy patient using a non-invasive electronic heart function measurement device intropic strain rate and inotropic electrical mechanical interval at rest and over a range of exercise according to an exercise protocol, or a catecholamine drug infusion protocol, to achieve a series of intropic steady-states of varying degrees of inotropy; plotting the natural logarithm of the absolute value of the inotropic strain rate against the reciprocal of said electrical-mechanical interval at rest and at each inotropic steady-state; with the result that said steady states appear as points in a linear function in {1/(E-M)ino, ln(abs(Inotropic Strain Rate))} space, with a well-defined slope and intercept for slope >0, said function being defined as said patient’s inotropic calibration curve; writing fitting parameters for said linear function as (Slope, Intercept) as (x,y) points in {Slope, Intercept} space; graphing (Slope, Intercept) of each of said patients in {Slope, Intercept} space, as a downward sloping linear function, with resulting universal inotropic fitting parameters slope and intercept being graphed as a universal inotropic intercept-slope tradeoff function, whereby any deviation from said function for an individual being evaluated for heart disease being an indication of inotropic heart failure.

“12. A method for determining a universal intercept-slope tradeoff function for lusitropic function comprising the steps of: selecting a number of heart healthy patients of diverse height, weight, age, and gender; measuring for each said healthy patient using a non-invasive electronic heart function measurement device lusitropic strain rate and lusitropic electrical mechanical interval at rest and over a range of exercise according to an exercise protocol, or a catecholamine drug infusion protocol, to achieve a series of lusitropic steady-states of varying degrees of lusitropy; plotting the natural logarithm of the absolute value of the lusitropic strain rate against the reciprocal of said electrical-mechanical interval at rest and at each lusitropic steady-state; with the result that said steady states appear as points in a linear function in {1/(E-M)ino, ln(abs(lusitropic Strain Rate))} space, with a well-defined slope and intercept for slope >0, said function being defined as said patient’s lusitropic calibration curve; writing fitting parameters for said linear function as (Slope, Intercept) as (x,y) points in {Slope, Intercept} space; graphing (Slope, Intercept) of each of said patients in {Slope, Intercept} space, as a downward sloping linear function, with resulting universal lusitropic fitting parameters slope and intercept being graphed as a universal lusitropic intercept-slope tradeoff function, whereby any deviation from said function for an individual being evaluated for heart disease being an indication of lusitropic heart failure.

“13. A non-transitory computer readable medium storing the universal tradeoff function for inotropic function.

“14. A non-transitory computer readable medium storing the universal tradeoff function for lusitropic function.”

URL and more information on this patent application, see: HIRSH, ROBERT ALAN. Non-Invasive System And Method For Detecting And Accurately Quantifying Subclinical And Clinical Systolic And Diastolic Heart Failure. U.S. Patent Application Number 20240008837, filed February 6, 2023 and posted January 11, 2024. Patent URL (for desktop use only): https://ppubs.uspto.gov/pubwebapp/external.html?q=(20240008837)&db=US-PGPUB&type=ids

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