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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>et al. Artificial Intelligence in Cardiology. Journal
of the American College of Cardiology. 2018. Vol. 71(23). P. 2668-2679.
https://doi.org/10.1016/j.jacc.2018.03.521
[32] Lupenko S. Rhythm</journal-title>
      </journal-title-group>
      <issn pub-type="ppub">1613-0073</issn>
    </journal-meta>
    <article-meta>
      <title-group>
        <article-title>signals⋆</article-title>
      </title-group>
      <contrib-group>
        <aff id="aff0">
          <label>0</label>
          <institution>Lyubomyr Mosiy</institution>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Ternopil Ivan Puluj National Technical University</institution>
          ,
          <addr-line>Ruska str., 56, Ternopil, 46001</addr-line>
          ,
          <country country="UA">Ukraine</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2019</year>
      </pub-date>
      <volume>71</volume>
      <fpage>2668</fpage>
      <lpage>2679</lpage>
      <abstract>
        <p>Cardiovascular diseases remain the leading cause of mortality worldwide, necessitating the development of advanced diagnostic methods for early detection and risk stratification. This study introduces a novel mathematical model for quantifying amplitude variability of electrocardiogram (ECG) characteristic waves based on cyclic random process theory. The proposed model V k ( m ) = A k ( m ) - A k ( m - 1) captures beat-to-beat amplitude variations of P, Q, R, S, and T waves, providing quantitative metrics for assessing cardiac electrical stability. Statistical analysis was performed on ECG recordings from three patient groups: conditionally healthy individuals, patients with extrasystole, and patients with incomplete left bundle branch block. The Kolmogorov-Smirnov test confirmed stationarity (p-values: 0.578-0.945), while the Anderson-Darling test validated normal distribution across all groups. Results revealed a 300-fold increase in variance for extrasystole patients (σ² = 0.8099) compared to controls (σ² = 0.0027), quantitatively reflecting electrical instability. Higher-order statistical moments (skewness and kurtosis) demonstrated distinct patterns for different pathologies, suggesting diagnostic specificity. The computational simplicity of the model enables real-time implementation in modern ECG monitoring systems. These findings establish amplitude variability as a complementary diagnostic biomarker to traditional heart rate variability, offering new insights into cardiac electrical heterogeneity. The confirmed statistical properties provide a robust foundation for developing automated diagnostic algorithms and machine learning applications in cardiology.</p>
      </abstract>
      <kwd-group>
        <kwd>eol&gt;electrocardiogram</kwd>
        <kwd>ECG amplitude variability</kwd>
        <kwd>cyclic random process</kwd>
        <kwd>cardiac diagnostics</kwd>
        <kwd>statistical analysis</kwd>
        <kwd>heart rate variability</kwd>
        <kwd>biomedical signal processing</kwd>
        <kwd>cardiovascular diseases</kwd>
        <kwd>stationarity</kwd>
        <kwd>Anderson-Darling test</kwd>
        <kwd>Kolmogorov-Smirnov test</kwd>
        <kwd>machine learning in cardiology</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>
        Electrocardiography remains a fundamental non-invasive diagnostic method for cardiovascular
diseases (CVD), providing rapid and reliable assessment of cardiac electrical activity [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Graphical
representation of electrocardiogram (ECG) signals serves as an indispensable tool for detecting a
wide spectrum of cardiac pathologies, from simple rhythm disturbances to complex structural heart
diseases [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. ECG waveforms and temporal intervals contain important diagnostic information that
enables medical professionals to identify deviations from normal cardiac function [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
      </p>
      <p>Despite significant progress in automated ECG analysis, existing methods predominantly focus
on static characteristics of individual cardiac cycles or temporal intervals between characteristic
points. Traditional heart rate variability analysis is limited to RR interval investigation, neglecting
amplitude dynamics that may contain additional diagnostic information about myocardial electrical
stability. Meanwhile, complex nonlinear analysis methods, such as entropy measures or fractal
analysis, often lack direct clinical interpretation, complicating their practical application. This creates
a need for developing new mathematical models that would combine high diagnostic sensitivity with
interpretation simplicity and the possibility of integration into existing cardiac monitoring systems.</p>
      <p>The aim of this work is to develop and validate a mathematical model of ECG wave amplitude
variability based on cyclic random process theory for identifying additional diagnostic features of
cardiovascular diseases. Section 2 presents a review of current ECG modeling and analysis methods.
Section 3 describes the proposed mathematical model of amplitude variability and statistical analysis
methodology. Section 4 presents experimental verification results of the model on real clinical data
for various pathological conditions. The final section summarizes the obtained results and outlines
prospects for further research.</p>
    </sec>
    <sec id="sec-2">
      <title>2. Related Work and Mathematical Foundations</title>
      <p>
        The development of mathematical ECG models creates a theoretical foundation for deeper
understanding of cardiac electrophysiological processes and improving diagnostic accuracy [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ].
Researchers have developed diverse modeling approaches—from elementary descriptions of
individual signal components to complex simulations of the cardiac electrical conduction system [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ].
      </p>
      <p>
        Basic approaches include approximation of main ECG elements—P wave, QRS complex, and T
wave—using mathematical functions, particularly Gaussian distributions or polynomial expressions,
enabling automated recognition and quantitative assessment of signal parameters [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ]. Evaristo and
colleagues presented an autoregressive model based on a system of differential equations that
successfully generates tachograms and ECG signals with high correspondence to experimental data
[
        <xref ref-type="bibr" rid="ref7">7</xref>
        ]. Further development of this direction is presented in the work of Reis and colleagues, who
improved the McSharry model by adding noise components for realistic reproduction of pathological
conditions [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ].
      </p>
      <p>
        Special attention deserves the work of Ukrainian scientists in the field of cyclic random processes.
Lupenko developed the theory of rhythm-adaptive methods for statistical estimation of probabilistic
characteristics of cyclic processes, proving their advantage over classical approaches for ECG
analysis [
        <xref ref-type="bibr" rid="ref10 ref9">9, 10</xref>
        ]. The cyclic discrete random process model with temporal rhythm function, proposed
in works [
        <xref ref-type="bibr" rid="ref10 ref9">9, 10</xref>
        ], effectively accounts for both the cyclic nature of cardiac signals and their stochastic
variability. The conditional linear cyclostationary and multivariate random processes have been
analyzed in [
        <xref ref-type="bibr" rid="ref11 ref12">11, 12</xref>
        ] with application to biomedical signal modelling. Researchers [
        <xref ref-type="bibr" rid="ref13">13–15</xref>
        ] extended
these approaches for vector analysis of synchronously registered cardiac signals of different physical
nature.
      </p>
      <p>The effectiveness of automated cardiac diagnostic systems critically depends on the quality of
extracting relevant diagnostic features from electrocardiogram signals [16]. Modern approaches use
three main categories of characteristics: temporal, frequency, and morphological parameters.</p>
      <p>Temporal parameters include measurements of duration and intervals between main ECG
components. The RR interval serves as a basic metric for assessing heart rate variability and detecting
arrhythmias [17]. Precise determination of individual cardiac cycle boundaries constitutes a critically
important initial stage of automated analysis [18]. Analysis of amplitude characteristics and
durations of main waves allows detection of chamber hypertrophy, conduction blocks, and
myocardial ischemic changes [19].</p>
      <p>Heart rate variability (HRV), assessed by time and frequency domain methods, provides important
information about the state of autonomic cardiac regulation [20]. Poincaré plots represent an
effective tool for visualization and quantitative assessment of heart rhythm asymmetry [21].</p>
      <p>Spectral ECG analysis through Fourier and wavelet transforms reveals signal energy distribution
across frequency bands [22]. These methods allow identification of dominant frequency components
and detection of pathological spectral patterns characteristic of specific cardiac conditions.</p>
      <p>ECG waveform shape and amplitude contain diagnostically significant information about
myocardial electrical activity [23]. Accurate R-peak detection is crucial for correct heart rate
calculation, while using HRV information helps eliminate false detections [24]. Morphological
parameters are sensitive to changes in impulse conduction velocity, repolarization processes, and
ventricular activation sequences.</p>
      <p>
        Integration of advanced signal processing technologies with mathematical modeling has
significantly improved ECG interpretation capabilities [25]. Wavelet analysis methods demonstrate
high efficiency in studying time-frequency characteristics of cardiac signals [22, 26]. Application of
Q-wavelet transform with tunable parameters allows adaptation of analysis to specific features of
different arrhythmia types [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ].
      </p>
      <p>Spatial modeling of electrical impulse propagation through cardiac muscle provides
understanding of arrhythmia mechanisms [27]. Such models integrate detailed anatomical data and
electrophysiological properties of cardiomyocytes [28], helping to determine optimal zones for
catheter ablation [26].</p>
      <p>The combination of physical elements (sensors), digital systems, and the Internet of Things (IoT
devices) for continuous or periodic measurement of physiological parameters of the body, such as
ECG, together with computational elements (algorithms, software), provide automated collection,
analysis, and interpretation of biomedical data in real time [36, 37].</p>
      <p>
        Revolutionary changes in ECG analysis are associated with the implementation of deep learning
methods, which demonstrate classification accuracy up to 99% [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]. Convolutional neural networks
(CNN) and their modifications successfully recognize complex patterns without the need for manual
feature engineering [29]. Hybrid architectures, such as CNN-Transformer and neuro-fuzzy systems,
combine advantages of different approaches [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ].
      </p>
      <p>AI integration into clinical practice opens opportunities for early disease detection through
remote monitoring and development of personalized therapeutic strategies [30]. The use of large data
arrays, including medical images, electronic health records, and genomic information, allows AI
systems to identify complex patterns for risk prediction [31].</p>
      <p>Further development of rhythm-adaptive methods for cyclic signal analysis opens new horizons
for more accurate modeling and processing of ECG with irregular rhythm [32–34]. Adaptive methods
for estimating discrete rhythmic structures using various interpolation techniques increase the
accuracy of cyclic biomedical signal processing [35].</p>
    </sec>
    <sec id="sec-3">
      <title>3. Proposed Mathematical Model of Amplitude Variability of ECS waves</title>
      <p>The investigation of ECG wave amplitude variability indicators in each cardiac cycle enables the
detection of hidden pathological states in cardiovascular system functioning. Application of
mathematical modeling methods allows development of effective methods for studying ECG
amplitude variability based on its mathematical model to identify additional diagnostic features of
CVD.</p>
      <p>
        To model the amplitude variability of ECG waves (which is modeled as a random process [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]), a
set I = {P, Q, R, S, T} is introduced, representing the types of characteristic signal waves. For each type
of wave m ∈ Z, the amplitude value Ak ( ω , m) , ω∈ Ω (where Ω is the space of elementary events)
is determined, which represents the amplitude (which is a random variable) of the corresponding
wave within the corresponding cardiac cycle. The mathematical model of amplitude variability is
presented in the form of a random function V k ( ω , m), which takes into account the amplitude values
of the characteristic teeth of the ECG:
      </p>
      <p>V k ( ω , m) = Ak ( ω , m) - Ak ( ω , m - 1) ,
k ∈ {P , Q , R , S , T },
m∈ Z,
(1)
where Ak ( ω , m) – amplitude of the k-th type peak in the m-th cardiac cycle (mV);
Ak ( ω , m - 1) – amplitude of the k-th type peak in the previous valid cardiac cycle (mV);
V k ( ω , m) – the value of the amplitude variability function of ECG waves, reflecting the change in the
amplitude of the k-th type wave between the current m and the previous cardiac cycle (m-1).
Further, to simplify the text, we will omit the variable ω in the notation of random functions.</p>
      <p>
        For quantitative characterization of V k ( m) and its diagnostic evaluation [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ], a statistical
processing method was used, which enables the calculation of the following statistical indicators:
      </p>
      <sec id="sec-3-1">
        <title>The average value of V k ( m) for the k-th type of peaks:</title>
      </sec>
      <sec id="sec-3-2">
        <title>2. Standard deviation V k ( m):</title>
      </sec>
      <sec id="sec-3-3">
        <title>Coefficient of variation V k ( m):</title>
      </sec>
      <sec id="sec-3-4">
        <title>Range of values (variation range) V k ( m):</title>
        <p>μV ( k ) =
1 M</p>
        <p>∑ V k ( m) .</p>
        <p>M m=1
σ V ( k ) = √ M m=1
1 M</p>
        <p>∑ (V k ( m) - μV ( k ))2 .</p>
        <p>C V V ( k ) =</p>
        <p>× 100 % .
σ V ( k )
|μV ( k )|
Range (V k ( m)) = max V k ( m) - min V k ( m) .
m m
(2)
(3)
(4)
(5)</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>3.1. Statistical analysis of amplitude variability properties</title>
      <p>To validate the proposed mathematical model and assess its suitability for further diagnostic analysis,
a comprehensive statistical study of the properties of the amplitude variability function V k ( m) was
conducted. The statistical analysis included two critically important aspects: verification of process
stationarity and analysis of conformity to normal distribution.</p>
    </sec>
    <sec id="sec-5">
      <title>3.2. Stationarity test</title>
      <p>The stationarity of a random process is a fundamental property that determines the constancy of its
statistical characteristics over time. To test the hypothesis of stationarity of amplitude variability, the
two-sample Kolmogorov-Smirnov test was used. This nonparametric criterion allows comparing the
empirical distribution functions of two samples without any prior assumptions about the type of
distribution.</p>
      <p>The testing procedure consisted of dividing the time series V k ( m) into two equal parts and
comparing their distributions. The null hypothesis H₀ states that both samples come from the same
distribution, which indicates the stationarity of the process. At a significance level of α = 0.05, if
pvalue &gt; α, the null hypothesis is not rejected, confirming stationarity.</p>
      <p>




</p>
    </sec>
    <sec id="sec-6">
      <title>3.2.1.Analysis of normality of distribution</title>
      <p>Determining the type of amplitude variability distribution is critical for selecting adequate methods
of statistical analysis and interpretation of diagnostic signs. To test the hypothesis of normality of
distribution, the Anderson-Darling goodness-of-fit test was used, which is characterized by high
sensitivity to deviations in the tails of the distribution, which is especially important for detecting
rare pathological conditions.</p>
      <p>The Anderson-Darling goodness-of-fit test is based on comparing the empirical distribution
function with the theoretical normal distribution function. The test statistic A² is calculated taking
into account the quadratic deviations weighted by the variance. At a significance level of 0.05, if the
test statistic is less than the critical value, the hypothesis of normality is not rejected.</p>
    </sec>
    <sec id="sec-7">
      <title>3.2.2.Results of statistical analysis</title>
      <p>Analysis of amplitude variability indicators was performed for three groups of patients with different
cardiac conditions: healthy, with extrasystole, and with incomplete left bundle branch block. The test
results are presented in Figures 1–3.</p>
      <p>For healthy patients (Ch_2_P_FAV_nr):</p>
      <p>Kolmogorov-Smirnov test: p-value = 0.578, which significantly exceeds the significance level
of 0.05, confirming the stationarity of the process.</p>
      <p>Anderson-Darling goodness-of-fittest: test statistic = 0.721 is less then critical value = 0.752,
indicating compliance with normal distribution.</p>
      <p>Statistical characteristics: mean = 0.0000, variance = 0.0027, skew = 0.3196, kurtosis = 2.2285
autocorrelation function of V P ( m), the filled area represents the bounds± 1.96 / √ M for testing the
hypothesis that P-wave amplitude variability function is stationary white noise.</p>
      <p>For patients with extrasystole (Ch_2_P_FAV_es):</p>
      <p>Kolmogorov-Smirnov test: p-value = 0.808, confirms stationarity.</p>
      <p>Anderson-Darling test: test statistic = 0.309 is less then critical value = 0.743, corresponds to
normal distribution.</p>
      <p>Statistical characteristics: mean = 0.0147, variance = 0.8099, skew = 0.3048, kurtosis = -0.5394
of the autocorrelation function of V P ( m), the filled area represents the bounds± 1.96 / √ M .</p>
      <p>For patients with incomplete blockage of the left bundle branch of the His bundle
(Ch_2_P_FAV_mb1):


</p>
      <p>Kolmogorov-Smirnov test: p-value = 0.945, highest stationarity among the studied groups.
Anderson-Darling test: test statistic = 0.290 is less then critical value = 0.75, corresponds to
normal distribution</p>
      <p>Statistical characteristics: mean = 0.0101, variance = 0.0020, skew = 0.6509, kurtosis = 1.2413
of the left bundle branch of the His bundle, b) estimation of the autocorrelation function of V P ( m),
the filled area represents the bounds± 1.96 / √ M .</p>
    </sec>
    <sec id="sec-8">
      <title>3.3. Interpretation of results</title>
      <p>The confirmed stationarity of amplitude variability for all studied patient groups demonstrates the
stability of statistical process properties over time, which is a necessary condition for applying
classical spectral analysis and forecasting methods. This allows the use of averaged statistical
characteristics as reliable diagnostic features, independent of the ECG registration moment.</p>
      <p>The correspondence to normal distribution of amplitude variability has important clinical
significance. First, it justifies the application of parametric statistical methods, which are
characterized by higher power compared to non-parametric analogues. Second, distribution
normality allows the use of the three-sigma rule for detecting anomalous values that may indicate
pathological conditions.</p>
      <p>The identified differences in statistical characteristics between patient groups demonstrate the
diagnostic potential of the proposed model. In particular, the significant increase in variance for the
extrasystole group (0.8099 versus 0.0027 for normal) reflects increased instability of cardiac electrical
activity. Changes in skewness and kurtosis coefficients may also serve as additional markers of
specific pathologies.</p>
      <p>Thus, the results of statistical analysis confirm the adequacy of the proposed mathematical model
of ECG amplitude variability and justify the possibility of its use for developing new diagnostic
criteria for cardiovascular diseases.</p>
    </sec>
    <sec id="sec-9">
      <title>4. Results/Discussions</title>
      <p>The statistical analysis of amplitude variability function V k ( m) revealed significant quantitative
differences between patient groups, validating the diagnostic potential of the proposed mathematical
model. The most prominent finding was a 300-fold increase in variance for patients with extrasystole
(σ² = 0.8099) compared to the control group (σ² = 0.0027), quantitatively reflecting the electrical
instability characteristic of arrhythmic conditions. In contrast, patients with incomplete left bundle
branch block maintained variance levels (σ² = 0.0020) comparable to controls, suggesting that
conduction abnormalities primarily affect temporal rather than amplitude characteristics. Analysis of
higher-order moments provided additional discriminatory features: the extrasystole group exhibited
negative excess kurtosis (γ₂ = -0.5394), indicating a platykurtic distribution with fewer extreme
values, while the incomplete LBBB group showed the highest skewness (γ₁ = 0.6509) with positive
excess kurtosis (γ₂ = 1.2413), corresponding to intermittent but intense amplitude variations
characteristic of sporadic conduction delays.</p>
      <p>The confirmed stationarity (p-values: 0.578-0.945) and normality of amplitude variability across
all groups enable robust parametric diagnostic criteria development and application of the
threesigma rule for pathological outlier detection. These findings establish amplitude variability as a
complementary diagnostic metric to traditional heart rate variability analysis, capturing orthogonal
information about cardiac electrical stability. The computational simplicity of the model (Equation 1)
facilitates real-time implementation in modern ECG monitoring systems, while the clear physical
interpretation of variance as electrical instability enhances clinical adoption. The distinct statistical
patterns observed for different pathologies suggest that amplitude variability metrics could serve as
input features for machine learning classifiers, potentially achieving high diagnostic accuracy for
early arrhythmia detection and risk stratification.</p>
      <p>Future research should focus on validating these findings in larger, diverse cohorts to establish
population-specific reference ranges and diagnostic thresholds. Extension to multi-lead
synchronized analysis could reveal spatial patterns of electrical heterogeneity, while integration with
existing ECG analysis protocols would enhance diagnostic capabilities in ambiguous cases where
traditional morphological assessment yields inconclusive results.</p>
    </sec>
    <sec id="sec-10">
      <title>Conclusion</title>
      <p>This study presents a novel mathematical model for quantifying amplitude variability of ECS
characteristic waves based on cyclic random process theory. The proposed model
V k ( m) = Ak ( m) - Ak ( m - 1) successfully captures beat-to-beat amplitude variations, providing a
quantitative framework for assessing cardiac electrical stability. Statistical validation confirmed both
stationarity (p-values: 0.578-0.945) and normality of the amplitude variability function across
different cardiac conditions, establishing a robust foundation for parametric diagnostic analysis.</p>
      <p>The key finding of a 300-fold increase in variance for extrasystole patients compared to controls
demonstrates the model’s sensitivity to pathological electrical instability. The distinct statistical
signatures observed-including variance, skewness, and kurtosis patterns-for different cardiac
conditions (normal, extrasystole, incomplete LBBB) indicate that amplitude variability metrics can
serve as effective diagnostic biomarkers complementary to traditional ECS parameters. The
computational simplicity and clear physical interpretation of these metrics facilitate their integration
into existing ECS analysis systems and enable real-time monitoring applications.</p>
      <p>Future work should focus on validating these findings in larger, diverse patient populations to
establish standardized diagnostic thresholds and reference ranges. The confirmed statistical
properties of amplitude variability open pathways for machine learning integration and automated
diagnosis systems. This research contributes to the advancement of quantitative ECS analysis by
introducing a mathematically rigorous, clinically interpretable method for characterizing dynamic
cardiac electrical behavior, ultimately supporting more accurate and timely diagnosis of
cardiovascular disorders.</p>
    </sec>
    <sec id="sec-11">
      <title>Declaration on Generative AI</title>
      <p>During the preparation of this work, the authors used Grammarly in order to grammar and spell
check, and improve the text readability. After using the tool, the authors reviewed and edited the
content as needed to take full responsibility for the publication’s content.
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