Method and system for evaluating stability of cardiac propagation reserve

Abstract

A method of determining the susceptibility to ventricular arrhythmias in a subject, comprises the steps of: (a) collecting (e.g., by surface EKG or intracardiac EKG) at least one QT and DI interval data set from the subject during a stage of gradually increasing heart rate or a stage of gradually decreasing heart rate; (b) determining (e.g., by applying low- and high pass filtering) low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals in said at least one QT and DI interval data set; (c) finding a plurality of correlated and anti-correlated portions between said high-frequency QT-DI fluctuation signals; (d) determining corresponding regression lines for said correlated and anti-correlated portions; (e) finding a plurality of (or in some embodiments all) steady state QT-DI points designated by intersections between said low frequency QT-DI trends and said corresponding regression lines; (f) fitting action potential durations computed from a rate dependent reaction-diffusion model to corresponding ones of said steady state QT-DI points to give (i) a model excitation threshold and (ii) a minimal level of refractoriness at a plurality of (or in some embodiments all of) said steady state QT-DI points; (g) at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the difference between said minimal level of refractoriness and a model critical excitation threshold for a stable solitary pulse corresponding to the rate dependent reaction diffusion model of step (f) to give a reserve of refractoriness (RoR); (h) fitting action potential durations computed from a rate dependent reaction-diffusion model to said correlated and anti-correlated portions to give a rate of adaptation of each model excitation threshold to a corresponding steady state value at a plurality of (or in some embodiments all of) said steady state QT-DI points; (i) at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the inverse of said rate of adaptation to give a reserve of memory (RoM); (j) combining said reserve of refractoriness (RoR) and said reserve of memory (RoM) to produce a metric of stability-of-propagation reserve (SoPR) in said subject, a higher value of SoPR indicating lower susceptibility to ventricular arrhythmias in said subject. Systems and apparatus for carrying out the method are also described.

That which is claimed is: 
     
         1 . A method of determining the susceptibility to ventricular arrhythmias in a subject, comprising the steps of:
 (a) collecting at least one QT and DI interval data set from the subject during a stage of gradually increasing heart rate or a stage of gradually decreasing heart rate;   (b) determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals in said at least one QT and DI interval data set;   (c) finding a plurality of correlated and anti-correlated portions between said high-frequency QT-DI fluctuation signals;   (d) determining corresponding regression lines for said correlated and anti-correlated portions;   (e) finding a plurality of steady state QT-DI points designated by intersections between said low frequency QT-DI trends and said corresponding regression lines;   (f) fitting action potential durations computed from a rate dependent reaction-diffusion model to corresponding ones of said steady state QT-DI points to give (i) a model excitation threshold and (ii) a minimal level of refractoriness at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (g) at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the difference between said minimal level of refractoriness and a model critical excitation threshold for a stable solitary pulse corresponding to the rate dependent reaction diffusion model of step (f) to give a reserve of refractoriness (RoR);   (h) fitting action potential durations computed from a rate dependent reaction-diffusion model to said correlated and anti-correlated portions to give a rate of adaptation of each model excitation threshold to a corresponding steady state value at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (i) at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the inverse of said rate of adaptation to give a reserve of memory (RoM);   (j) combining said reserve of refractoriness (RoR) and said reserve of memory (RoM) to produce a metric of stability-of-propagation reserve (SoPR) in said subject, a higher value of SoPR indicating lower susceptibility to ventricular arrhythmias in said subject.   
     
     
         2 . The method of  claim 1 , wherein said step (a) of collecting at least one QT and DI interval data set is carried out by surface EKG or intracardiac EKG. 
     
     
         3 . The method of  claim 1 , wherein said step (b) of determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals is carried out by applying low- and high pass filtering. 
     
     
         4 . The method of  claim 1 , wherein said step (d) of determining corresponding regression lines for said correlated and anti-correlated portions is carried out by linear regression analysis. 
     
     
         5 . The method of  claim 1 , wherein said action potential durations are from 100 to 900 milliseconds in duration. 
     
     
         6 . The method of  claim 1 , wherein said model excitation threshold (dimensionless) is from 0.05 to 1. 
     
     
         7 . The method of  claim 1 , wherein said minimal level of refractoriness (dimensionless) is from 0.05 to 1. 
     
     
         8 . The method of  claim 1 , wherein said highest heart rate in said QT and DI interval data set is 300 beats per minute. 
     
     
         9 . The method of  claim 1 , wherein said model critical excitation threshold for a stable solitary pulse (dimensionless) is from 0.1 to 1. 
     
     
         10 . The method of  claim 1 , wherein said reserve of refractoriness (dimensionless) is from zero to one. 
     
     
         11 . The method of  claim 1 , wherein said rate of adaptation of each model excitation threshold (dimensionless) is 0.01 to 1. 
     
     
         12 . The method of  claim 1 , wherein said reserve of memory (dimensionless) is from 1 to 100. 
     
     
         13 . The method of  claim 1 , wherein said stability-of-propagation reserve (dimensionless) is from zero to one. 
     
     
         14 . A method of determining susceptibility to ventricular arrhythmias in a subject, comprising the steps, performed on a computer system, of:
 (a) providing at least one QT and DI interval data set collected from the subject during a stage of gradually increasing heart rate or a stage of gradually decreasing heart rate;   (b) determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals in said at least one QT and DI interval data set;   (c) finding a plurality of correlated and anti-correlated portions between said high-frequency QT-DI fluctuation signals;   (d) determining corresponding regression lines for said correlated and anti-correlated portions;   (e) finding a plurality of steady state QT-DI points designated by intersections between said low frequency QT-DI trends and said corresponding regression lines;   (f) fitting action potential durations computed from a rate dependent reaction-diffusion model to corresponding ones of said steady state QT-DI points to give (i) a model excitation threshold and (ii) a minimal level of refractoriness at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (g) at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the difference between said minimal level of refractoriness and a model critical excitation threshold for a stable solitary pulse corresponding to the rate dependent reaction diffusion model of step (f) to give a reserve of refractoriness (RoR);   (h) fitting action potential durations computed from a rate dependent reaction-diffusion model to said correlated and anti-correlated portions to give a rate of adaptation of each model excitation threshold to a corresponding steady state value at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (i) at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the inverse of said rate of adaptation to give a reserve of memory (RoM);   (j) combining said reserve of refractoriness (RoR) and said reserve of memory (RoM) to produce a metric of stability-of-propagation reserve (SoPR) in said subject, a higher value of SoPR indicating lower susceptibility to ventricular arrhythmias in said subject.   
     
     
         15 . The method of  claim 14 , wherein said step (b) of determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals is carried out by applying low- and high pass filtering. 
     
     
         16 . The method of  claim 14 , wherein said step (d) of determining corresponding regression lines for said correlated and anti-correlated portions is carried out by linear regression analysis. 
     
     
         17 . The method of  claim 14 , wherein:
 said action potential durations are from 100 to 900 milliseconds in duration;   said model excitation threshold (dimensionless) is from 0.05 to or 1;   said minimal level of refractoriness (dimensionless) is from 0.05 to 1;   said highest heart rate in said QT and DI interval data set is 300 beats per minute;   said model critical excitation threshold for a stable solitary pulse (dimensionless) is from 0.1 to 1;   said reserve of refractoriness (dimensionless) is from zero to one;   said rate of adaptation of each model excitation threshold (dimensionless) is 0.01 to 1;   said reserve of memory (dimensionless) is from 1 to 100; and   said stability-of-propagation reserve (dimensionless) is from zero to one.   
     
     
         18 . A computer system for determining susceptibility to ventricular arrhythmias in a subject, said system comprising:
 (a) means for providing at least one QT and DI interval data set collected from the subject during a stage of gradually increasing heart rate or a stage of gradually decreasing heart rate;   (b) means for determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals in said at least one QT and DI interval data set;   (c) means for finding a plurality of correlated and anti-correlated portions between said high-frequency QT-DI fluctuation signals;   (d) means for determining corresponding regression lines for said correlated and anti-correlated portions;   (e) means for finding a plurality of steady state QT-DI points designated by intersections between said low frequency QT-DI trends and said corresponding regression lines;   (f) means for fitting action potential durations computed from a rate dependent reaction-diffusion model to corresponding ones of said steady state QT-DI points to give (i) a model excitation threshold and (ii) a minimal level of refractoriness at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (g) means for, at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the difference between said minimal level of refractoriness and a model critical excitation threshold for a stable solitary pulse corresponding to the rate dependent reaction diffusion model of step (f) to give a reserve of refractoriness (RoR);   (h) means for fitting action potential durations computed from a rate dependent reaction-diffusion model to said correlated and anti-correlated portions to give a rate of adaptation of each model excitation threshold to a corresponding steady state value at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (i) means for, at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the inverse of said rate of adaptation to give a reserve of memory (RoM);   (j) means for combining said reserve of refractoriness (RoR) and said reserve of memory (RoM) to produce a metric of stability-of-propagation reserve (SoPR) in said subject, a higher value of SoPR indicating lower susceptibility to ventricular arrhythmias in said subject.   
     
     
         19 . The system method of  claim 18 , wherein said means for (b) of determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals comprises means for applying low- and high pass filtering. 
     
     
         20 . The system of  claim 18 , wherein said means for (d) of determining corresponding regression lines for said correlated and anti-correlated portions comprises means for linear regression analysis. 
     
     
         21 . The system of  claim 18 , wherein:
 said action potential durations are from 100 to 900 milliseconds in duration;   said model excitation threshold (dimensionless) is from 0.05 to 1;   said minimal level of refractoriness (dimensionless) is from 0.05 to 1;   said highest heart rate in said QT and DI interval data set is 300 beats per minute;   said model critical excitation threshold for a stable solitary pulse (dimensionless) is from 0.1 to 1;   said reserve of refractoriness (dimensionless) is from zero to one;   said rate of adaptation of each model excitation threshold (dimensionless) is 0.01 to 1;   said reserve of memory (dimensionless) is from 1 to 100; and   said stability-of-propagation reserve (dimensionless) is from zero to one.   
     
     
         22 . A computer program product for determining susceptibility to ventricular arrhythmias in a subject from (a) at least one QT and DI interval data set collected from the subject during a stage of gradually increasing heart rate or a stage of gradually decreasing heart rate, said computer program product comprising a computer usable storage medium having computer readable program code means embodied in the medium, the computer readable program code means comprising:
 (b) computer readable program code means for determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals in said at least one QT and DI interval data set;   (c) computer readable program code means for finding a plurality of (or in some embodiments all) correlated and anti-correlated portions between said high-frequency QT-DI fluctuation signals;   (d) computer readable program code means for determining corresponding regression lines for said correlated and anti-correlated portions;   (e) computer readable program code means for finding a plurality of (or in some embodiments all) steady state QT-DI points designated by intersections between said low frequency QT-DI trends and said corresponding regression lines;   (f) computer readable program code computer readable program code means for fitting action potential durations computed from a rate dependent reaction-diffusion model to corresponding ones of said steady state QT-DI points to give (i) a model excitation threshold and (ii) a minimal level of refractoriness at a plurality of (or in some embodiments all of) said steady state QT-DI points;   (g) computer readable program code means for, at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the difference between said minimal level of refractoriness and a model critical excitation threshold for a stable solitary pulse corresponding to the rate dependent reaction diffusion model of step (f) to give a reserve of refractoriness (RoR);   (h) computer readable program code means for fitting action potential durations computed from a rate dependent reaction-diffusion model to said correlated and anti-correlated portions to give a rate of adaptation of each model excitation threshold to a corresponding steady state value at a plurality of said steady state QT-DI points;   (i) computer readable program code means for, at the steady state QT-DI point corresponding to the highest heart rate in said QT and DI interval data set, determining the inverse of said rate of adaptation to give a reserve of memory (RoM);   (j) computer readable program code means for combining said reserve of refractoriness (RoR) and said reserve of memory (RoM) to produce a metric of stability-of-propagation reserve (SoPR) in said subject, a higher value of SoPR indicating lower susceptibility to ventricular arrhythmias in said subject.   
     
     
         23 . The product of  claim 22 , wherein said computer readable program code means for (b) of determining low-frequency QT-DI interval trends and high-frequency QT-DI fluctuation signals comprises means for applying low- and high pass filtering. 
     
     
         24 . The product of  claim 22 , wherein said computer readable program code means for (d) of determining corresponding regression lines for said correlated and anti-correlated portions comprises means for linear regression analysis. 
     
     
         25 . The product of  claim 22 , wherein:
 said action potential durations are from 100 to 900 milliseconds in duration;   said model excitation threshold (dimensionless) is from 0.05 to 1;   said minimal level of refractoriness (dimensionless) is from 0.05 to 1;   said highest heart rate in said QT and DI interval data set is 300 beats per minute;   said model critical excitation threshold for a stable solitary pulse (dimensionless) is from 0.1 to 1;   said reserve of refractoriness (dimensionless) is from zero to one;   said rate of adaptation of each model excitation threshold (dimensionless) is 0.01 to 1;   said reserve of memory (dimensionless) is from 1 to 100; and   said stability-of-propagation reserve (dimensionless) is from zero to one.