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.

Description

FIELD OF THE INVENTION[0001]The present invention concerns methods, systems and apparatus for detecting risk of ventricular arrhythmias in a subject.BACKGROUND OF THE INVENTION[0002]Each year approximately 310,000 Americans die of sudden cardiac death (SCD) from ventricular tachyarrhythmias [Lloyd-Jones 2009]. The first preventive step toward reducing mortality from SCD is to identify individuals at risk for developing arrhythmias. Yet, despite years of research, the risk stratification strategies are unclear and there are still no reliable clinical tests that predict who is susceptible to this potentially lethal heart rhythm disorders [Kusmirek & Gold 2007].[0003]Currently, the most reliable method of assessing vulnerability to cardiac arrhythmias is EP testing, in which a provocative intracardiac pacing protocol is applied to the patient with an aim of inducing an arrhythmia episode [Daubert 2006]. EP testing is an invasive procedure and carries a non-negligible risk of death. In ...

AI Technical Summary

Benefits of technology

[0051]An advantage of the present invention over the Starobin-Chernyak method is that their aggregate index depends on the slope of the steady state restitution curve, which is not reliable indicator of stability of propagation [Ideker 2002]. For example, the magnitude of this index can vary due to flattening of restitution curves during myocardial ischemia [Franz 2003], which prevents the accurate assessment of instabilities. Indeed, the index decreases at higher heart rates when propagation of the excitation wave is more prone to instabilities caused by enhanced interactions with spatial inhomogeneities during ischemia. Our initial model-based investigation of SoPR shows that the present invention will be free from this limitation.

[0052]Other major non-invasive methods of assessing an individual's susceptibility to cardiac arrhythmias include different types of assessment of the QT and / or RR interval variability, both spatial and temporal (U.S. Patents by Chamoun U.S. Pat. No. 5,020,540, 1991; Wang No. U.S. Pat. No. 4,870,974, 1989; Kroll et al. U.S. Pat. No. 5,117,834, 1992; Henkin et al. U.S. Pat. No. 5,323,783, 1994; Xue et al. U.S. Pat. No. 5,792,065, 1998; Lander U.S. Pat. No. 5,827,195, 1998; Lander et al. U.S. Pat. No. 5,891,047, 1999; Hojum et al. U.S. Pat. No. 5,951,484, 1999). These methods are different from the present invention because they are linked to specific types of spatial and temporal inhomogeneities. Thus, in contrast to SoPR, they cannot predict instabilities that are developing in structurally homogeneous cardiac muscle.

[0053]The present invention is explained in greater detail in the drawings herein and the specification set forth below.

Problems solved by technology

Yet, despite years of research, the risk stratification strategies are unclear and there are still no reliable clinical tests that predict who is susceptible to this potentially lethal heart rhythm disorders [Kusmirek & Gold 2007].

EP testing is an invasive procedure and carries a non-negligible risk of death.

Thus, the risk to the patient is well below the risk of current EP testing.

However, alternans is only one possible route to a fatal arrhythmia (FIG. 1).

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