METHOD OF DETECTING PARAMETERS INDICATIVE OF ACTIVATION OF SYMPATHETIC AND PARASYMPATHETIC NERVOUS SYSTEMS

Abstract

Computer-implemented method of detecting parameters indicative of a variation of activation of the sympathetic nervous system and of a variation of activation of the parasympathetic nervous system in a subject in a transition from a basal condition to a perturbed condition, comprising the calculation of the power ratio between the powers in the LF and HF bands of the power spectra of the systolic time interval and the diastolic time interval.

Claims

1. A computer-implemented method of detecting parameters indicative of a variation of activation of sympathetic nervous system and of a variation of activation of parasympathetic nervous system in a subject in a transition from a basal condition to a perturbed condition, comprising the following steps: A. receiving a discrete pressure signal p(t.sub.i) of the subject comprising a plurality of heartbeats; B. identifying each heartbeat of the discrete pressure signal p(t.sub.i) and, within each heartbeat, identifying a systolic phase p.sub.sys(t.sub.i) and a diastolic phase p.sub.dia(t.sub.i); C. building a diagram D.sub.sys of duration of the systolic phase as a function of a heartbeat progressive number and a diagram D.sub.dia of duration of the diastolic phase as a function of the heartbeat progressive number; D. executing a resampling of the diagram D.sub.sys of duration of the systolic phase, obtaining a resampled diagram D.sub.sys.sup.(r), of duration of the systolic phase, and a resampling of the diagram D.sub.dia of duration of the diastolic phase, obtaining a resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase; E. calculating a power spectrum PSD.sub.sys of the resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase and a power spectrum PSD.sub.dia of the resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase at frequencies between a lower limit frequency f.sub.lower_limit and a upper limit frequency f.sub.upper_limit higher than the lower limit frequency f.sub.lower_limit; F. calculating a power P.sub.LF.sup.(PSD.sup.sys.sup.) of the power spectrum PSD.sub.sys in a LF band, a power P.sub.HF.sup.(PSD.sup.sys.sup.) of the power spectrum PSD.sub.sys in a HF band, a power P.sub.LF.sup.(PSD.sup.dia.sup.) in the LF band of the power spectrum PSD.sub.dia, and a power P.sub.HF.sup.(PSD.sup.dia.sup.) in the HF band of the power spectrum PSD.sub.dia, wherein the frequency f.sub.LF in the LF band is higher than or equal to a first intermediate frequency f.sub.intermediate_1 and lower than a second intermediate frequency f.sub.intermediate_2, thereby
f.sub.intermediate_1≤f.sub.LF<f.sub.intermediate_2, wherein the lower limit frequency f.sub.lower_limit is lower than the first intermediate frequency f.sub.intermediate_1, that is in turn lower than the second intermediate frequency f.sub.intermediate_2, that is in turn lower than the upper limit frequency f.sub.upper_limit, thereby
f.sub.lower_limit<f.sub.intermediate_1<f.sub.intermediate_2<f.sub.upper_limit, and wherein the frequency f.sub.HF in the HF band is higher than or equal to the second intermediate frequency f.sub.intermediate_2 and lower than the upper limit frequency f.sub.upper_limit, thereby
f.sub.intermediate_2≤f.sub.HF<f.sub.upper_limit; and G. calculating and outputting a value of a ratio LHR.sub.sys between the powers in the LF and HF bands of the power spectrum PSD.sub.sys and a value of a ratio LHR.sub.dia between the powers in the LF and HF bands of the power spectrum PSD.sub.dia, thereby ${\mathrm{LHR}}_{\mathrm{sys}}=\frac{P_{\mathrm{LF}}^{\left({\mathrm{PSD}}_{sys}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{sys}\right)}}$ ${\mathrm{LHR}}_{\mathrm{dia}}=\frac{P_{LF}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}$ wherein steps A-G of the computer-implemented method are executed on the subject first in a basal condition and then in a perturbed condition.

2. The computer-implemented method according to claim 1, wherein the lower limit frequency f.sub.lower_limit is equal to 0.01 Hz, the upper limit frequency f.sub.upper_limit ranges from 0.4 Hz to 1.2 Hz, the first intermediate frequency f.sub.intermediate_1 ranges from 0.04 Hz to 0.12 Hz, and the second intermediate frequency f.sub.intermediate_2 ranges from 0.15 Hz to 0.45 Hz, wherein optionally the upper limit frequency f.sub.upper_limit ranges from 0.8 Hz to 1.2 Hz, the first intermediate frequency f.sub.intermediate_1 ranges from 0.08 Hz to 0.12 Hz, and the second intermediate frequency f.sub.intermediate_2 ranges from 0.30 Hz to 0.45 Hz, wherein more optionally the upper limit frequency t.sub.upper_limit is equal to 1.2 Hz, the first intermediate frequency f.sub.intermediate_1 is equal to 0.12 Hz, and the second intermediate frequency f.sub.intermediate_2 is equal to 0.45 Hz.

3. The computer-implemented method according to claim 1, wherein, in step E, the power spectra PSD.sub.sys and PSD.sub.dia are calculated through a Fourier transform, optionally through a Fast Fourier Transform (FFT), of the resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase and of the resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase, respectively.

4. The computer-implemented method according to claim 1, wherein the discrete pressure signal p(t.sub.i) received in step A has a time duration of at least 3 minutes, optionally of at least 4 minutes, more optionally of at least 5 minutes.

5. The computer-implemented method according to claim 1, wherein, in step B, the systolic phase and the diastolic phase of each heartbeat are identified on the basis of identification of the dicrotic notch time.

6. The computer-implemented method according to claim 5, that: in step B, further identifies a value of dicrotic notch pressure P.sub.dic in each heartbeat; in step C, further builds a diagram D.sub.dic of dicrotic notch pressure as a function of the heartbeat progressive number; in step D, further executes a resampling of the diagram D.sub.dic of dicrotic notch pressure obtaining a resampled diagram D.sub.dic.sup.(r) of dicrotic notch pressure; in step E, further calculates a power spectrum PSD.sub.dic of the resampled diagram D.sub.dic.sup.(r) of dicrotic notch pressure at frequencies between the lower limit frequency f.sub.lower_limit and the upper limit frequency f.sub.upper_limit; in step F, further calculates a power P.sub.LF.sup.(PSD.sup.dic.sup.) of the power spectrum PSD.sub.dic in the LF band and a power P.sub.HF.sup.(PSD.sup.dic.sup.) of the power spectrum PSD.sub.dic in the HF band; and in step G, further calculates and outputs a value of a ratio LHR.sub.dic between the powers in the LF and HF bands of the power spectrum PSD.sub.dic, thereby: ${\mathrm{LHR}}_{\mathrm{dic}}=\frac{P_{\mathrm{LF}}^{\left({\mathrm{PSD}}_{\mathrm{dic}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{dic}}\right)\stackrel{.}{\_}}}$

7. Computer-implemented method according to claim 1, wherein in step C the diagram D.sub.sys of duration of the systolic phase and the diagram D.sub.dia of duration of the diastolic phase are built by expressing the duration of the systolic phase and of the diastolic phase of each heartbeat as value normalised to an overall duration of the heartbeat under consideration.

8. Computer-implemented method according to claim 1, further comprising determining and outputting a HRV (Heart Rate Variability) of the subject first in the basal condition and then in the perturbed condition.

9. Computer-implemented method according to claim 1, that further calculates a standard deviation SD.sup.(sys) of the resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase and a standard deviation SD.sup.(dia) of the resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase, outputting them in step G, of the subject first in the basal condition and then in the perturbed condition.

10. Computer-implemented method according to claim 1, that further calculates a total power TP.sup.(sys) of the power spectrum PSD.sub.sys of the resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase and a total power TP.sup.(dia) of the power spectrum PSD.sub.dia of the resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase, outputting them in step G, of the subject first in the basal condition and then in the perturbed condition.

11. An apparatus comprising a processing unit configured to execute a computer-implemented method of detecting parameters indicative of a variation of activation of sympathetic nervous system and of a variation of activation of parasympathetic nervous system in a subject in a transition from a basal condition to a perturbed condition, comprising the following steps: A. receiving a discrete pressure signal p(t.sub.i) of the subject comprising a plurality of heartbeats; B. identifying each heartbeat of the discrete pressure signal p(t.sub.i) and, within each heartbeat, identifying a systolic phase p.sub.sys(t.sub.i) and a diastolic phase p.sub.dia(t.sub.i); C. building a diagram D.sub.sys of duration of the systolic phase as a function of a heartbeat progressive number and a diagram D.sub.dia of duration of the diastolic phase as a function of the heartbeat progressive number; D. executing a resampling of the diagram D.sub.sys of duration of the systolic phase, obtaining a resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase, and a resampling of the diagram D.sub.dia of duration of the diastolic phase, obtaining a resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase; E. calculating a power spectrum PSD.sub.sys of the resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase and a power spectrum PSD.sub.dia of the resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase at frequencies between a lower limit frequency f.sub.lower_limit and a upper limit frequency f.sub.upper_limit higher than the lower limit frequency f.sub.lower_limit; F. calculating a power P.sub.LF.sup.(PSD.sup.sys.sup.) of the power spectrum PSD.sub.sys in a LF band, a power P.sub.HF.sup.(PSD.sup.sys.sup.) of the power spectrum PSD.sub.sys in a HF band, a power P.sub.LF.sup.(PSD.sup.dia.sup.) in the LF band of the power spectrum PSD.sub.dia, and a power P.sub.HF.sup.(PSD.sup.dia.sup.) in the HF band of the power spectrum PSD.sub.dia, wherein the frequency f.sub.LF in the LF band is higher than or equal to a first intermediate frequency f.sub.intermediate_1 and lower than a second intermediate frequency f.sub.intermediate_2, thereby
f.sub.intermediate_1≤f.sub.LF<f.sub.intermediate_2, wherein the lower limit frequency f.sub.lower_limit is lower than the first intermediate frequency f.sub.intermediate_1, that is in turn lower than the second intermediate frequency f.sub.intermediate_2, that is in turn lower than the upper limit frequency f.sub.upper_limit, thereby
f.sub.lower_limit<f.sub.intermediate_1<f.sub.intermediate_2<f.sub.upper_limit, and wherein the frequency f.sub.HF in the HF band is higher than or equal to the second intermediate frequency f.sub.intermediate_2 and lower than the upper limit frequency f.sub.upper_limit, thereby
f.sub.intermediate_2≤f.sub.HF<f.sub.upper_limit; and G. calculating and outputting a value of a ratio LHR.sub.sys between the powers in the LF and HF bands of the power spectrum PSD.sub.sys and a value of a ratio LHR.sub.dia between the powers in the LF and HF bands of the power spectrum PSD.sub.dia, thereby ${\mathrm{LHR}}_{\mathrm{sys}}=\frac{P_{LF}^{\left({\mathrm{PSD}}_{\mathrm{sys}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{sys}}\right)}}{\mathrm{LHR}}_{\mathrm{dia}}=\frac{P_{LF}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}$ wherein steps A-G of the computer-implemented method are executed on the subject first in a basal condition and then in a perturbed condition.

12. (canceled)

13. A set of one or more computer-readable media having stored thereon a set of one or more computer programs comprising instructions which, when executed by one or more processing units, cause said one or more processing units to execute a computer-implemented method of detecting parameters indicative of a variation of activation of sympathetic nervous system and of a variation of activation of parasympathetic nervous system in a subject in a transition from a basal condition to a perturbed condition, comprising the following steps: A. receiving a discrete pressure signal p(t.sub.i) of the subject comprising a plurality of heartbeats; B. identifying each heartbeat of the discrete pressure signal p(t.sub.i) and, within each heartbeat, identifying a systolic phase p.sub.sys(t.sub.i) and a diastolic phase p.sub.dia(t.sub.i); C. building a diagram D.sub.sys of duration of the systolic phase as a function of a heartbeat progressive number and a diagram D.sub.dia of duration of the diastolic phase as a function of the heartbeat progressive number; D. executing a resampling of the diagram D.sub.sys of duration of the systolic phase, obtaining a resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase, and a resampling of the diagram D.sub.dia of duration of the diastolic phase, obtaining a resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase; E. calculating a power spectrum PSD.sub.sys of the resampled diagram D.sub.sys.sup.(r) of duration of the systolic phase and a power spectrum PSD.sub.dia of the resampled diagram D.sub.dia.sup.(r) of duration of the diastolic phase at frequencies between a lower limit frequency f.sub.lower_limit and a upper limit frequency f.sub.upper_limit higher than the lower limit frequency f.sub.lower_limit; F. calculating a power P.sub.LF.sup.(PSD.sup.sys.sup.) of the power spectrum PSD.sub.sys in a LF band, a power P.sub.HF.sup.(PSD.sup.sys.sup.) of the power spectrum PSD.sub.sys in a HF band, a power P.sub.LF.sup.(PSD.sup.dia.sup.) in the LF band of the power spectrum PSD.sub.dia, and a power P.sub.HF.sup.(PSD.sup.dia.sup.) in the HF band of the power spectrum PSD.sub.dia, wherein the frequency f.sub.LF in the LF band is higher than or equal to a first intermediate frequency f.sub.intermediate_1 and lower than a second intermediate frequency f.sub.intermediate_2, thereby
f.sub.intermediate_1≤f.sub.LF<f.sub.intermediate_2, wherein the lower limit frequency f.sub.lower_limit is lower than the first intermediate frequency f.sub.intermediate_1, that is in turn lower than the second intermediate frequency f.sub.intermediate_2, that is in turn lower than the upper limit frequency f.sub.upper_limit, thereby
f.sub.lower_limit<f.sub.intermediate_1<f.sub.intermediate_2<f.sub.upper_limit, and wherein the frequency f.sub.HF in the HF band is higher than or equal to the second intermediate frequency f.sub.intermediate_2 and lower than the upper limit frequency f.sub.upper_limit, thereby
f.sub.intermediate_2≤f.sub.HF<f.sub.upper_limit; and G. calculating and outputting a value of a ratio LHR.sub.sys between the powers in the LF and HF bands of the power spectrum PSD.sub.sys and a value of a ratio LHR.sub.dia between the powers in the LF and HF bands of the power spectrum PSD.sub.dia, thereby ${\mathrm{LHR}}_{\mathrm{sys}}=\frac{P_{\mathrm{LF}}^{\left({\mathrm{PSD}}_{\mathrm{sys}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{sys}}\right)}}{\mathrm{LHR}}_{\mathrm{dia}}=\frac{P_{LF}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}$ wherein steps A-G of the computer-implemented method are executed on the subject first in a basal condition and then in a perturbed condition.

Description

[0054] The present invention will be now described, for illustrative but not limiting purposes, according to its preferred embodiments, with particular reference to FIG. 1 of the accompanying drawings, that shows a flow graph of the preferred embodiment of the computer-implemented method according to the invention.

[0055] The inventor has surprisingly ascertained that, to obtain more information on the activation of the sympathetic nervous system and on the activation of the parasympathetic nervous system, as well as on the balance between them, in a subject on the basis of the variability of the heart rhythm, it is possible to exploit the coupling of heart to the arterial system. To this end, differently from ECG-based detection techniques, the computer-implemented method according to the invention is based on cardiac pressure cycles. The computer-implemented method according to the invention exploits the “mechanical” property of a heartbeat of being composed of two main phases, namely the systolic phase and the diastolic phase.

[0056] Differently, prior art methods and apparatuses, employing ECG signal detection, are based on cardiac cycles of electrical signal. Since the electrical signal of a cardiac cycle corresponds only to the electrical component of the electro-mechanical heart activity that is used to make the blood circulate inside the human body, it is not sufficient to provide all the available information on the balance of the sympathetic and parasympathetic nervous systems, since much of this information is related to the mechanical component of the cardiac activity that actually makes blood circulate. In fact, the electrical signal sent to the heart does not immediately produce a mechanical response of the heart itself, because this also depends on the inertia of the heart and cardiovascular system, i.e. on the specific state of rigidity and compliance of the various systems which form the cardiovascular system. This implies that the prior art methods and apparatuses employing the detection of the ECG signal to evaluate the HRV are affected by errors and approximations which greatly limit their reliability. By way of example, and not by way of limitation, the only electrical component of cardiac activity in the event that the aortic valve does not open correctly, creating problems of electromechanical coupling of the heart to the cardiovascular and respiratory systems, can provide a ECG signal that signals an adequate heartbeat through the detection of the electrical activity of the heart, while instead the mechanical functionality of the heart is strongly compromised and the sympathetic and parasympathetic nervous systems are consequently activated in an unbalanced way with respect to each other; this is applicable in all cases where there is a qualitative dissociation of the electrical component from the mechanical component of the cardiac activity.

[0057] The computer-implemented method according to the invention, thanks to the analysis of the variability of the duration separately for the systolic phase and for the diastolic phase of the cardiac cycles of pressure, allows to obtain a detection of parameters indicative of the variations of activation of the sympathetic nervous system and parasympathetic nervous system, from which it is also possible to evaluate a change in the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system, that allows a reliable evaluation of the activation of the sympathetic and parasympathetic nervous systems and of the degree of their balance. In fact, since the cardiac cycles of pressure have a typical pressure morphology, in which the systolic and diastolic phases are well defined, it is possible to distinguish and hence weigh the contributions to the HRV of the same systolic and diastolic phases and not only of the entire cardiac cycle, as it happens instead for the evaluation of the HRV through the analysis of the tachogram based on the R-R distance of an ECG signal of the prior art methods. In the following the variability of the duration of the systolic phase of the pressure signal will be indicated with SYS-V and the variability of the duration of the diastolic phase of the pressure signal will be indicated with DIA-V.

[0058] In particular, the separate analysis of the SYS-V and the DIA-V, carried out by the computer-implemented method according to the invention, can detect parameters indicative of the variations of activation of the sympathetic nervous system and parasympathetic nervous system and of a balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system that is different, in one of or both the systolic and diastolic phases, with respect to the balance evaluated by the detection of the HRV of the entire cardiac cycle based on the ECG signal of the prior art methods.

[0059] By way of example, and not by way of limitation, the same HRV could correspond to three different pairs of SYS-V and DIA-V for three respective subjects, namely corresponding to an athlete, a cardiopathic subject, and a normal subject. In fact, in general, even in the case where there are no variations in the R-R distance of an ECG signal in a plurality of cardiac cycles, there can be variations of opposite sign of the duration of the systolic phase and of the duration of the diastolic phase in the same plurality of cardiac cycles due to the adaptation of the organism to specific conditions to which it undergoes. Hence, the variability of these two systolic and diastolic phases can represent contributions of the activation of the sympathetic nervous system and of the activation of the parasympathetic nervous system which are different from each other, whereby the analysis of SYS-V and DIA-V provides more specific information on such contributions. Similarly, in the case where the heart rate of a subject is constant before and after an event, the two mechanical phases that form it, namely the systolic and diastolic phases, can change. In this way, the computer-implemented method according to the invention allows to identify in advance the need or not to cause changes in the contribution of the activation of the sympathetic nervous system with respect to that of the activation of the parasympathetic nervous system, for example through interventions on the component of the activation of the parasympathetic nervous system that affect and change the component of the activation of the sympathetic nervous system, such as the administration of vasoconstrictor or vasodilator or inotropic drugs.

[0060] Consequently, the degree of balance of the activation of the sympathetic nervous system and of the activation of the parasympathetic nervous system due to some pathological responses, both to drugs and surgical stresses, that prior art methods based on the ECG signal detection for the HRV measurement fail to identify correctly, is reliably evaluated by the analysis of the SYS-V and the DIA-V carried out by the computer-implemented method according to the invention. In particular, through the analysis of the SYS-V and the DIA-V, the computer-implemented method according to the invention is able to allow to early identify some pathological conditions when they are not yet overt, which the prior art methods identify only after their degeneration.

[0061] FIG. 1 shows a flow chart of the preferred embodiment of the computer-implemented method according to the invention.

[0062] In a first step 1000, the method receives a discrete pressure signal p(t.sub.i) (such as for example an arterial pressure or a pulmonary venous pressure or a central venous pressure) of a subject or patient comprising a plurality of heartbeats. In particular, the discrete pressure signal p(t.sub.i) can derive from a continuous pressure signal p(t) that is detected through pressure sensors and that is digitised to obtain the discrete signal p(t.sub.i) (wherein the index i indicates the succession of discrete samples), or a discrete signal (i.e. already digitised) stored in a memory medium; in particular, the detection of the continuous pressure signal p(t) can take place either invasively or non-invasively, e.g. through a photoplethysmographic sensor. The received discrete pressure signal p(t.sub.i) has a time duration optionally of at least 3 minutes, more optionally of at least 4 minutes, even more optionally of at least 5 minutes.

[0063] In a second step 1050, the method identifies each heartbeat of the discrete pressure signal p(t.sub.i) and, within each heartbeat, identifies the systolic phase p.sub.sys(t.sub.i) and the diastolic phase p.sub.dia(t.sub.i). Optionally, the method performs the identification of each heartbeat through the automated method of discrimination of the heartbeat described in the International application no. WO 2004/084088 A1, and/or the identification of the systolic phase and diastolic phase of each heartbeat on the basis of the identification of the dicrotic notch time (corresponding to the time of closure of the aortic valve for arterial pressure signals or to the time of closure of the tricuspid valve for pulmonary pressure signals).

[0064] In a third step 1100, the method builds a diagram D.sub.sys of the duration of the systolic phase (ordinate axis) as a function of the progressive number of the heartbeats (abscissa axis) and a diagram D.sub.dia of the duration of the diastolic phase (ordinate axis) as a function of the progressive number of the heartbeats (abscissa axis). The duration of the systolic phase and diastolic phase is optionally expressed in milliseconds.

[0065] In a fourth step 1150, the method performs a resampling of the diagram D.sub.sys of the duration of the systolic phase and of the diagram D.sub.dia of the duration of the diastolic phase (built in the third step 1100), obtaining a resampled diagram D.sub.sys.sup.(r) of the duration of the systolic phase and a resampled diagram D.sub.dia.sup.(r) of the duration of the diastolic phase.

[0066] In a fifth step 1200, the method calculates the power spectrum PSD.sub.sys of the resampled diagram D.sub.sys.sup.(r) of the duration of the systolic phase and the power spectrum PSD.sub.dia of the resampled diagram D.sub.dia.sup.(r) of the duration of the diastolic phase at frequencies between a lower limit frequency f.sub.lower_limit, optionally equal to 0.01 Hz, and an upper limit frequency f.sub.upper_limit (higher than the lower limit frequency f.sub.lower_limit), optionally variable from 0.4 Hz to 1.2 Hz, more optionally variable from 0.8 Hz to 1.2 Hz, even more optionally equal to 1.2 Hz; in particular, the lower limit frequency f.sub.lower_limit and the upper limit frequency f.sub.upper_limit depend on the type of the subjects under examination. Optionally, the method calculates the power spectra PSD.sub.sys and PSD.sub.dia through a Fourier transform, more optionally a Fast Fourier Transform (FFT), of the resampled diagram D.sub.sys.sup.(r) of the duration of the systolic phase and of the resampled diagram D.sub.dia.sup.(r) of the duration of the diastolic phase, respectively. Alternatively to the Fourier transform, other embodiments of the computer-implemented method according to the invention can calculate the power spectra PSD.sub.sys and PSD.sub.dia through an autoregressive modelling or through a wavelet transform.

[0067] In a sixth step 1250, the method subdivides each of the power spectra PSD.sub.sys and PSD.sub.dia into three frequency bands VLF (Very Low Frequency), LF (Low Frequency) and HF (High Frequency). In the LF band the frequency f.sub.LF ranges from a first intermediate frequency f.sub.intermediate_1 to a second intermediate frequency f.sub.intermediate_2, thereby

f.sub.intermediate_1≤f.sub.LF<f.sub.intermediate_2,

where the lower limit frequency f.sub.lower_limit is lower than the first intermediate frequency f.sub.intermediate_1, that in turn is lower than the second intermediate frequency f.sub.intermediate_2, that in turn is lower than the upper limit frequency f.sub.upper_limit, thereby

f.sub.lower_limit<f.sub.intermediate_1<f.sub.intermediate_2<f.sub.upper_limit.

In the HF band the frequency f.sub.HF ranges from the second intermediate frequency f.sub.intermediate_2 to the upper limit frequency f.sub.upper_limit, thereby

f.sub.intermediate_2≤f.sub.HF<f.sub.upper_limit.

In the VLF band the frequency f.sub.VLF ranges from the lower limit frequency f.sub.lower_limit to the first intermediate frequency f.sub.intermediate_1 thereby

f.sub.lower_limit≤f.sub.VLF<f.sub.intermediate_1.

The first intermediate frequency f.sub.intermediate_1 and the second intermediate frequency f.sub.intermediate_2 also depend on the type of the subjects under examination. Optionally, the first intermediate frequency f.sub.intermediate_1 ranges from 0.04 Hz to 0.12 Hz, more optionally it ranges from 0.08 Hz to 0.12 Hz, still more optionally it is equal to 0.12 Hz; optionally, the second intermediate frequency f.sub.intermediate_2 ranges from 0.15 Hz to 0.45 Hz, more optionally it ranges from 0.30 Hz to 0.45 Hz, still more optionally it is equal to 0.45 Hz.

[0068] Still in the sixth step 1250, the method calculates the power of each of the power spectra PSD.sub.sys and PSD.sub.dia in each one of the LF and HF bands; namely: [0069] the power P.sub.LF.sup.(PSD.sup.sys.sup.) in the LF band of the power spectrum PSD.sub.sys (given by the integral in the LF band, i.e. the summation in the discretised domain of frequencies of the power spectrum PSD.sub.sys); [0070] the power P.sub.HF.sup.(PSD.sup.sys.sup.) in the HF band of the power spectrum PSD.sub.sys (given by the integral in the HF band, i.e. the summation in the discretised domain of frequencies of the power spectrum PSD.sub.sys); [0071] the power P.sub.LF.sup.(PSD.sup.dia.sup.) in the LF band of the power spectrum PSD.sub.dia (given by the integral in the LF band, i.e. the summation in the discretised domain of frequencies of the power spectrum PSD.sub.dia); [0072] the power P.sub.HF.sup.(PSD.sup.dia.sup.) in the HF band of the power spectrum PSD.sub.dia (given by the integral in the HF band, i.e. the summation in the discretised domain of frequencies of the power spectrum PSD.sub.dia).

[0073] In a seventh step 1300, the method calculates (and outputs) the values of the ratios LHR.sub.sys and LHR.sub.dia between the powers in the LF and HF bands of the power spectra PSD.sub.sys and PSD.sub.dia, respectively, thereby:

[00003]${\mathrm{LHR}}_{\mathrm{sys}}=\frac{P_{\mathrm{LF}}^{\left({\mathrm{PSD}}_{\mathrm{sys}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{sys}}\right)}}{\mathrm{LHR}}_{\mathrm{dia}}=\frac{P_{\mathrm{LF}}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{dia}}\right)}}$

[0074] On the basis of the values of the ratios LHR.sub.sys and LHR.sub.dia output by the seventh step 1300, taking account of the type of population to which the subject belongs, a doctor is able to evaluate the variation of activation of the sympathetic nervous system and the variation of the activation of the parasympathetic nervous system, from which it is also possible to evaluate a variation in the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system (i.e., the possible predominance of the activity of the sympathetic nervous system or of the activity of the parasympathetic nervous system on the other) of the subject himself/herself. In particular, the values of the LHR.sub.sys and LHR.sub.dia ratios depend on the type of population, by age and pathology, to which the examined subjects belong.

[0075] In other words, the computer-implemented method according to the invention uses the characteristics of the mechanical response of the cardiovascular system to the electrical stimulus of the heart, analysing the systolic and diastolic phases within each cardiac cycle. This allows for a more reliable evaluation than prior art methods, since the dynamic components of the activations of the sympathetic and parasympathetic nervous system and the balance between the activation of the sympathetic nervous system and the activation of the parasympathetic nervous system give different indications of dynamic equilibrium during the two systolic and diastolic phases, providing more detailed information on stress and vagal activation.

[0076] The inventor made some evaluations on the results obtained by applying the computer-implemented method according to the invention and comparing the results with those obtained by the prior art methods in the evaluation of the HRV. In particular, the experiments were conducted on subjects who passed from a basal condition to a perturbed condition in which an event causes a change in the cardiovascular system.

[0077] The experiments show that the characteristics of variation of the HRV can be either in agreement or in disagreement with those of the resampled diagram D.sub.dia.sup.(r) of the duration of the diastolic phase (albeit with non-equal absolute values), and that the characteristics of variation of the resampled diagram D.sub.sys.sup.(r), of the duration of the systolic phase are often substantially different from those of the HRV.

[0078] Some evaluations were carried out on the results obtained for subjects for whom the perturbed condition was caused by the administration of a powerful anaesthetic that has a sympatholytic effect (namely Propofol®). According to traditional physiology, the ratio between the LF and HF components must decrease because the vagal activity is activated and, thus, by inhibiting the activity of the sympathetic nervous system, the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system changes. However, the characteristics of the HRV had variations that led to conflicting results in the ratio between the LF and HF components of the power spectrum PSD of the tachogram, resulting in a decrease in some subjects and an increase in others, demonstrating that the power spectrum PSD of the tachogram does not correctly identify the activation of the vagal nerve and the inhibition of the sympathetic nervous system. Differently, the ratio LHR.sub.sys derived from the resampled diagram D.sub.sys.sup.(r) of the duration of the systolic phase decreases for all patients, reliably identifying the prevalence of the activation of the parasympathetic nervous system with respect to the basal condition (i.e. to the condition not altered by the administration of the anaesthetic).

[0079] In general, the results obtained from the application of the computer-implemented method according to the invention revealed that, to evaluate which one of the sympathetic nervous system and the parasympathetic nervous system is activated in a prevalent way, it is sufficient to carry out a comparison of the variations of the ratios LHR.sub.sys and LHR.sub.dia in the transition from the basal condition to the perturbed condition in function of the type of subject examined. By way of example, for some types of subjects, if such variations are discordant, the activation of the parasympathetic nervous system has prevailed over the activation of the sympathetic nervous system, while if such variations are in agreement (e.g., both increase), the activation of the sympathetic nervous system has prevailed over the activation of the parasympathetic nervous system.

[0080] In the case of a patient under examination (e.g., a patient who has problems of orthostatism, which can lead to syncope, or a patient suffering from liver cirrhosis) and no data related to a basal condition are available, the evaluation of the variation in activation of the sympathetic nervous system and of the variation of the activation of the parasympathetic nervous system, as well as the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system, are carried out by performing the computer-implemented method according to the invention while the patient is lying down on an examination table, assuming this as the basal condition, subjecting the patient to the so-called tilt test (i.e., the examination table is raised by 60° degrees), assuming this as the perturbed condition, and performing again the computer-implemented method according to the invention. For a patient suffering from liver cirrhosis, it is sufficient to move from a supine position to an orthostatic position as perturbed condition.

[0081] It is important to underline that the computer-implemented method according to the invention is not a diagnostic method per se, but it is a method detecting parameters, namely the ratios LHR.sub.sys e LHR.sub.dia, indicative of the variation of activation of the sympathetic nervous system, of the variation of activation of the parasympathetic nervous system, and of a balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system of a subject in the transition from a basal condition to a perturbed condition, which require a subsequent interpretation by a physician for formulating the diagnosis.

[0082] Other embodiments of the computer-implemented method according to the invention can also: [0083] in the second step 1050, identify the value of the dicrotic notch pressure P.sub.dic in each heartbeat; [0084] in the third step 1100, build a diagram D.sub.dic of the dicrotic notch pressure (ordinate axis) as a function of the progressive number of the heartbeats (abscissa axis); [0085] in the fourth step 1150, perform a resampling the diagram D.sub.dic of the dicrotic notch pressure obtaining a resampled diagram D.sub.dic.sup.(r) of the dicrotic notch pressure; [0086] in the fifth step 1200, calculate the power spectrum PSD.sub.dic (optionally through a Fourier transform, more optionally a FFT, or through an autoregressive modelling or through a wavelet transform) of the resampled diagram D.sub.dic.sup.(r) of the dicrotic notch pressure at frequencies ranging from the lower limit frequency f.sub.lower_limit (optionally equal to 0.01 Hz), and the upper limit frequency f.sub.upper_limit (higher than the lower limit frequency f.sub.lower_limit and optionally ranging from 0.4 Hz to 1.2 Hz, more optionally ranging from 0.8 Hz to 1.2 Hz, still more optionally equal to 1.2 Hz), that, as mentioned, depend on the type of the subjects examined; [0087] in the sixth step 1250, subdivide the power spectrum PSD.sub.dic of the resampled diagram D.sub.dic.sup.(r) of the dicrotic notch pressure into three frequency bands VLF (in which the frequency f.sub.VLF ranges from the lower limit frequency f.sub.lower_limit to the first intermediate frequency f.sub.intermediate_1), LF (in which the frequency f.sub.LF ranges from the first intermediate frequency f.sub.intermediate_1 to the second intermediate frequency f.sub.intermediate_2) and HF (in which the frequency f.sub.HF ranges from the second intermediate frequency f.sub.intermediate_2 to the upper limit frequency f.sub.upper_limit), and it calculate, in each of the LF and HF bands, the power of the power spectrum PSD.sub.dic, namely the power P.sub.LF.sup.(PSD.sup.dic.sup.) of the power spectrum PSD.sub.dic in the LF band (given by the integral in the LF band, i.e. the summation in the discretised domain of the frequencies, of the power spectrum PSD.sub.dic) and the power P.sub.HF.sup.(PSD.sup.dic.sup.) of the power spectrum PSD.sub.dic in the HF band (given by the integral in the HF band, i.e. the summation in the discretised domain of the frequencies, of the power spectrum PSD.sub.dic); as mentioned, the first intermediate frequency f.sub.intermediate_1 and the second intermediate frequency f.sub.intermediate_2 depend on the type of the subjects examined: optionally, the first intermediate frequency f.sub.intermediate_1 ranges from 0.04 Hz to 0.12 Hz, more optionally it ranges from 0.08 Hz to 0.12 Hz, still more optionally it is equal to 0.12 Hz; optionally, the second intermediate frequency f.sub.intermediate_2 ranges from 0.15 Hz to 0.45 Hz, more optionally it ranges from 0.30 Hz to 0.45 Hz, still more optionally it is equal to 0.45 Hz; [0088] in the seventh step 1300, calculate (and output) the value of the ratio LHR.sub.dic between the powers in the LF and HF bands of the power spectrum PSD.sub.dic, thereby:

[00004]${\mathrm{LHR}}_{\mathrm{dic}}=\frac{P_{\mathrm{LF}}^{\left({\mathrm{PSD}}_{\mathrm{dic}}\right)}}{P_{\mathrm{HF}}^{\left({\mathrm{PSD}}_{\mathrm{dic}}\right)}}$

whereby a doctor is able to evaluate the variation of activation of the sympathetic nervous system and the variation of activation of the parasympathetic nervous system as well as the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system of a subject also on the basis of the value of the ratio LHR.sub.dic, taking into account the type of population to which the subject belongs.

[0089] Further embodiments of the computer-implemented method according to the invention can also determine the HRV according to conventional techniques, whereby: [0090] in the third step 1100, building a tachogram D.sub.beat of the discrete pressure signal p(t.sub.i); [0091] in the fourth step 1150, performing a resampling of the tachogram D.sub.beat of the discrete pressure signal p(t.sub.i) obtaining a resampled tachogram D.sub.beat.sup.(r) of the discrete pressure signal p(t.sub.i); [0092] in the fifth step 1200, calculating the power spectrum PSD.sub.beat (optionally through a Fourier transform, more optionally a FFT, or through an autoregressive modelling or through a wavelet transform) of the resampled tachogram D.sub.beat.sup.(r) of the discrete pressure signal p(t.sub.i) at frequencies between 0.01 Hz and 0.4 Hz; [0093] in the sixth step 1250, subdividing the power spectrum PSD.sub.beat of the resampled tachogram D.sub.beat.sup.(r) of the discrete pressure signal p(t.sub.i) into three frequency bands VLF_HRV (in which the frequency f.sub.VLF_HRV ranges from 0.01 Hz to 0.04 Hz), LF_HRV (in which the frequency f.sub.LF_HRV ranges from 0.04 Hz to 0.15 Hz) e HF_HRV (in which the frequency f.sub.HF_HRV ranges from 0.15 Hz to 0.4 Hz), and calculating, in each one of the bands LF_HRV e HF_HRV, the power of the power spectrum PSD.sub.beat, namely the power P.sub.LF_HRV.sup.(PSD.sup.beat.sup.) in the LF_HRV band of the power spectrum PSD.sub.beat (given by the integral in the LF_HRV band, i.e. the summation in the discretised domain of the frequencies, of the power spectrum PSD.sub.beat) and the power P.sub.HF_HRV.sup.(PSD.sup.beat.sup.) in the HF_HRV band of the power spectrum PSD.sub.beat (given by the integral in the HF_HRV band, i.e. the summation in the discretised domain of the frequencies, of the power spectrum PSD.sub.beat); and [0094] in the seventh phase 1300, calculating (and outputting) the value of the ratio LHR.sub.beat between the peak frequencies in the LF_HRV and HF_HRV bands of the power spectrum PSD.sub.beat, thereby:

[00005]${\mathrm{LHR}}_{\mathrm{beat}}=\frac{P_{\mathrm{LF\_HRV}}^{\left({\mathrm{PSD}}_{beat}\right)}}{P_{\mathrm{HF\_HRV}}^{\left({\mathrm{PSD}}_{beat}\right)}}$

whereby a physician is able to evaluate the variation of activation of the sympathetic nervous system and the variation of activation of the parasympathetic nervous system as well as the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system of a subject also on the basis of the value of the ratio LHR.sub.beat, taking into account the type of population to which the subject belongs.

[0095] Other embodiments of the computer-implemented method according to the invention can also: [0096] calculate (optionally in any one of the steps from the fifth step 1200 to the seventh step 1300, and outputting in the seventh step 1300) the standard deviation SD.sup.(sys) of the resampled diagram D.sub.sys.sup.(r) of the duration of the systolic phase and the standard deviation SD.sup.(dia) of the resampled diagram D.sub.dia.sup.(r) of the duration of the diastolic phase (and possibly the standard deviation SD.sup.(beat) of the resampled tachogram D.sub.beat.sup.(r) of the discrete pressure signal p(t.sub.i)), and optionally the total power TP.sup.(sys) of the power spectrum PSD.sub.sys of the resampled diagram D.sub.sys.sup.(r) of the duration of the systolic phase and the total power TP.sup.(dia) of the power spectrum PSD.sub.dia of the resampled diagram D.sub.dia.sup.(r) of the duration of the diastolic phase (and possibly the total power TP.sup.(beat) of the power spectrum PSD.sub.beat of the resampled tachogram D.sub.beat.sup.(r) of the discrete pressure signal p(t.sub.i)),
whereby a physician, taking into account the type of population to which a subject belongs, is able to evaluate the variation of activation of the sympathetic nervous system and the variation of activation of the parasympathetic nervous system as well as the balance between the activity of the sympathetic nervous system and the activity of the parasympathetic nervous system of the subject himself/herself also on the basis of the value of the standard deviations SD.sup.(sys) and SD.sup.(dia) (and possibly of the standard deviation SD.sup.(beat)), and optionally also on the basis of the total powers TP.sup.(sys) and TP.sup.(dia) (as well as of the total power TP.sup.(beat)).

[0097] Further embodiments of the computer-implemented method according to the invention can build, in the third step 1100, the diagram D.sub.sys of the duration of the systolic phase and the diagram D.sub.dia of the duration of the diastolic phase expressing the duration of the systolic phase and of the diastolic phase of each heartbeat as a normalised value (e.g., as a percentage value) with respect to the overall heartbeat duration, rather than as an absolute value in milliseconds.

[0098] In the above, the preferred embodiments have been described and a number of variations of the present invention have been suggested, but it is to be understood that those skilled in the art can make other variations and changes without departing from the scope of protection thereof, as defined by the appended claims.